`OF BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS
`AND THEIR IMPLICATIONS FOR ANTI-
`BODY COMPLEMENTARITY*
`
`BY TAI TE WU, PH.D., AND ELVIN A. KABAT, PH.D
`(From the Departmetits of Microbiology, Neurology, and H1tmati Genetics and Develop
`mem, College of Physicia11,s and Surgems, Columbia Utiiversity, and the Ne1iro
`logical fostitute, Presbyteriati Hospital, New York 10032; the Biomathematics
`Divisioti, Grad1ro.te School of Medical Sciemes, Comell University and the
`Sloan-Kettering Instiifite, New York 10021)
`(Received for publication 26 March 1970)
`
`The extraordinary versatility of the antibody-forming mechanism in producing an
`almost limitless number of specific receptor sites complementary for almost any molec
`ular conformation of matter within a size range (1-3) represented by a hexa- or hepta
`saccharide as an upper and a mono- or disaccharide as a lower limit, is almost certainly
`related to the unique structural features of immunoglobulins and difierentiates them
`from all other known proteins. These antibody-combining sites are formed as a con
`sequence of the interaction of two polypeptide chains, a light and a heavy chain (2, 4,
`5). The antibodies usually formed to various antigens often represent heterogeneous
`populations of immunoglobulin molecules of different classes, subclasses, and genetic
`variants and also show specificities t�ward different antigenic determinants (1, 2, 6, 7).
`In some instances, however, relatively homogeneous populations of antibodies with
`respect to many of these properties have been obtained. Among these have been human
`antibodies to dextran and levan (8, 9) and rabbit antibodies to the group-specific carbo
`hydrate of streptococcus (10-12), antibodies to the Type III-specific capsular poly
`saccharide of pneumococcus (13, 14), rabbit antihapten (15), and specimens of anti
`bodies and of Fab' fragments which crystallized (Nisonoff et al., in references 16, 17),
`but sequence data on these are not yet available.
`The large body of sequence data related to immunoglobulin structure comes from
`the analysis of urinary Bence Jones proteins and from the monoclonal immunoglobu
`lins found in large amounts in the sera of patients with multiple myeloma and Walden
`strom macroglobulinemia (16, 18). While a substantial body of evidence was available
`relating these proteins to immunoglobulins, the recent demonstration that many
`myeloma globulins have specific ligand-binding properties like those of many anti
`bodies provides increasing confidence that myeloma globulins represent homogeneous
`populations of antibody molecules (16, 18-27). The ability to produce in BALB/c
`
`* Aided by grants from the National Science Foundation (GB-8341) and the National
`Cancer Institute (CA-08748), and a general Research Support Grant of the U. S. Public
`Health Service.
`
`211
`
`1 of 40
`
`BI Exhibit 1053
`
`
`
`212
`
`.BENCE JONES PROTEINS AND MYELOMA LIGFr1' CHAINS
`
`mice myelomas and macroglobulinemias (28) which produce myeloma globulins and
`Bence Jones proteins like those in the human, provides a source of data Crom which
`important evolutionary trends can be inferred.
`Thus the extensive sequence data on Bence Jones proteins, which are considered to
`be light chains of myeloma globulins and Waldenstrom macroglobulins (29), and on
`various light and heavy chains, provide information clearly pertinent to the problem
`of the elucidation of the structure of antibody-combining sites.
`The unique finding that distinguishes the immunoglobulins from all other proteins is
`that the N-terminal half of the light chains and the N-terminal quarter of the heavy
`chains vary in sequence in samples obtained from individual monoclonal immuno
`globulins and that indeed no two such variable regions of any chain and no two mye
`loma immunoglobulins or Bence Jones proteins have thus far been found to be identical
`in sequence (30). The constant region, however, is essentially no different from other
`proteins in that the variation in the amino acidc; found at any position is ascribable
`to species and class variations or to genetic variants such as Inv factors. By com
`parison of sequence data on the variable and constant regions of Bence Jones proteins
`with amino acid composition of purified human antibodies, it could be shown that
`most of the compositional variation could only originate in the variable region (see
`Kabat in reference 18).
`From sequence data, a variety of hypotheses have been ad vanced (7, 31-35) to
`explain the structural basis of antibody complementarity. All of these are selective
`theories, i.e. they consider that the information for complementarity is essentially built
`into the primary sequence of each chain and that a given antigen only triggers the
`biosynthesis of those antibody molecules having complementary receptor sites. There
`are two types of selective theories: germ line theories (36) and somatic mutation
`theories (37-39). At present no hypothesis is generally accepted. Excellent reviews
`(sec above) arc available.
`
`The present communication is an extension of earlier efforts from this labora
`tory (18, p. 87, and 40-43) to locate more precisely those portions of the vari
`able region which are directly responsible for antibody complementarity, that
`is which make direct contact with the antigenic determinant, and to explain
`the unique capacity of these proteins to have so many complementary regions.
`As in the earlier studies, all human K, human X, and mouse K .Bence Jones
`protein and light chain sequences are aligned for maximum homology (44)
`and all variable regions are considered as a unit and compared with the con
`stant regions. These earlier studies had called attention to the following:
`(a) The variable regions had fe:w if any species-specific positions while the
`constant regions of the human and mouse proteins had 36 species-specific
`amino acid substitutions per 107 residues (40, 45). A species-specific position
`is defined as one at which the amino acid residues in the mouse proteins differ
`from tl1ose in the human proteins.
`(b) When the invariant residues of these two regions were compared, the
`latest tabulation (45) showed the variable regions to have 10 invariant and
`almost invarianl glycines and no invariant alanines, leucines, valines, histi-
`
`2 of 40
`
`BI Exhibit 1053
`
`
`
`TAI TE WU AND ELVIN A. KABAT
`
`213
`
`dines, lysines, or serines while lhe constant regions had 3 each of invariant
`alanine, leucine, and valine, and 2 invariant histidines, 2 invariant lysines, and
`5 invariant serines. It was suggested that the invariant glycines were important
`in contributing to the flexibility needed by the variable region in accommo
`dating the numerous substitutions (41, 43) at the variable positions. It was
`also suggested that the invariant glycines near the end of the variable region
`at positions 99 and 101, plus the almost invariant glycine at position 100,
`provided a pivot upon which the complementarity-determining regions might
`move to make better contact with the antigenic determinant (43; 18, p. 87)
`just as the walls of the lysozyme site have been shown to adjust somewhat to
`accommodate its hexasaccharide substrate (46). The hydrophobic residues in
`the constant region were hypothesized to be involved in noncovalent bonding
`to the heavy chain.
`(c) From an examination of sequences of the KI, KII, and K!II subgroups
`(Hood et al. in reference 16) (47, 48) of the human Bence Jones proteins in
`which many of the proteins in a subgroup had an identical sequence for the
`first 20-24 residues, it was postulated that there are two kinds of residues in
`the variable regions, those making direct contact with the antigenic determi
`nant (complementarity determining) and those which are involved only in
`three-dimensional folding (42). The latter would be expected to have less
`stringent requirements, and more mutation noise would be permitted than
`with the complementarity-determining residues. This distinction led to the
`inspection of the sequences for short stretches showing very high variability
`and two of these were identified: the most variable beginning at residue 89
`and ending at 97, the other running from residue 24 through 34. Each of these
`two unusually highly variable regions began after an invariant half-cystine
`and was followed by an invariant phenylalanine (residue 98) and an invariant
`tryptophane (residue 35) respectively. It is of interest thal the two regions are
`brought close together by the S-S bond I2:rlI88 (45). Milstein (47), Milstein
`and Pink (7), and Franek (49) have also called attention to the highly variable
`positions in these regions and Franek (49) has noted an additional highly
`variable region around residues 52-55. It was hypothesized (45) that these first
`two regions might represent the complementarity-determining regions and
`that complementarity might be acquired by the insertion of small linear se
`quences into the light and heavy chains by some episomal or other insertion
`mechanism. It is striking that the differences in chain length seen in the Bence
`Jones proteins ar� confined to these two regions of the chain. The remaining
`portions of each chain would be essentially under the control of structural
`genes. The inserted sequences would be drawn from a large but finite set and
`either inserted under the influence of antigen, if antibody-forming cells are
`multipotent, or individual sequences might be distributed to immunoglobulin-
`
`3 of 40
`
`BI Exhibit 1053
`
`
`
`214
`
`BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS
`
`formfog cells during differentiation iI the capacity of individual cells to synthe
`size antibody is restricted.
`This working hypothesis offers several advantages:
`(a) It is capable of providing the evolutionary stability and accounts for
`the universality of the antibody-forming mechanism throughout the verte
`brates. Germ line theories (34-36) postulate one gene for each of the thousand
`or more variable regions (30). This would be expected to result in divergence
`during evolution since the loss by mutation of any one variable region would
`only minimally affect the capacity to form antibody and survival; thus indi
`viduals and populations lacking certain variable regions would arise.
`(b) It offers a substantial simplification to the problem of producing a very
`large number of complementary sites. While it is known that in all proteins
`with specific receptors the site is formed by residues from widely separated
`portions of the chain, these sites are all formed by single chains. Thus, form
`ing a three-dimensional site must involve residues from various regions. The
`antibody site being formed by a heavy and a light chain need not necessarily
`be so restricted.
`Since much additional data on the light chains and a number of heavy chain
`sequences have been accumulated, the present communication represents a
`further attempt at analyzing the unique features of the variable regions of
`immunoglobulin chains. Among aspects considered are the role of glycine,
`invariant residues, and hydrophobicity patterns, and the highly variable por
`tions, with a view to localizing the regions responsible for complementarity
`and evaluating various theories in terms of evolutionary origin and perpetua
`tion of the antibody-forming mechanism.
`Sequence Data Employed-Complete and partial sequence data have been
`published on 77 Bence Jones proteins and immunoglobulin light chains as well
`as on a number of heavy chains. Data were available on 24 human KI, 4 human
`K!I, 17 human KlII, 10 human >..I, 2 human >..II, 6 human >..III, 5 human >..IV,
`2 human ;\ V, 2 mouse Kl, and 5 mouse Kil proteins.1
`
`The original light chain sequence data may be found in the following references.
`HBJ 98: Baglioni, C. 1967. Bioc/re;m. Biophys. Res. Commun. 26:82.
`Eu: Cunningham, B. A., P. D. Gottlieb, W. H. Konigsberg, and G. M. Edelman. 1968.
`Biochemistry. 7:1983.
`Mil (human Kil): Dreyer, W. J., W. R. Gray, and L. Hood. 1967. Cold Spring Harbor
`Symp. Qtiant. Biol. 32:353.
`Hae, Dob, Pal: Grant, A., and L. Hood. Unpublished work.
`Roy, Cum: Hilschman, N., and L. C. Craig. 1965. Proc. Nat A cad. Sci. U.S. A. 63:1403;
`
`Hilschmann, N. 1967. Hoppe-Seyler's z. Pltysiol. Chem. 348:1077; Hilschmann, N.,
`H. U. Barnikol, M. Hess, B. Langer, H. Ponstingl, M. Steinmetz-Kayne, L. Suter, and
`S. Watanabe. 1968. Fed. Ettr. Biochem. Soc. Symp., 5t!t. In press.
`
`1 The World Health Organization has recently changed the notation of subgroups so that
`human Kil in this paper will become human �Ill and human K!II will become human KIL
`
`4 of 40
`
`BI Exhibit 1053
`
`
`
`TAl TE WU AND ELVIN A. I<ABAl'
`
`215
`
`HS 78, HS 92, HS 94, HS 68, HS 70, HS 77, HS 86, HS 24: Hood, L., and D. Ein. 1968.
`Nature (Londo1i). 220:764.
`HBJ 7, HBJ 11, HBJ 2, HBJ 8: Hood, L., W. R. Gray, and W. ]. Dreyer. 1966. J. Mo/.
`Biol. 22:179.
`MBJ 41, MBJ 70, MBJ 6: Hood, L., W. R. Gray, and W. ]. Dreyer. 1966. Proc. Nat'l
`Acad. Sci. U.S. A. 66:826.
`HBJ 10, HBJ 1, HBJ 4, HBJ 6, HBJ 5, HS 4, HBJ 12, HS 6, HBJ 15: Hood, L., W. R.
`Gray, B. G. Sanders, and W. ]. Dreyer. 1967. Cold Spring Harbor Symp. Quant. Biol.
`32:133.
`Ste: Edman, P., and A. G. Cooper. 1968 Fed. Eur. Biochem Soc. Letters. 2:33; Hood, L.,
`and D. W. Talmage. 1969. In Developmental Aspects of Antibody Formation and
`Structure. Prague. In press.
`Lay, Mar, Ioe, Wa.g, How, Koh: Kaplan, A. P. and H. Metzger. 1969. Bwclzenzistry. 10:
`3944.
`New, III, Mil (human XIV): Langer, B., M. Steinmetz-Kayne, and N. Hi!schmann. 1968.
`I!oppe-Seyler's z. Physiol. Chem. 349:945.
`BJ, Ker: Milstein, C. 1966. Biochem. J. 101:352.
`Rad, fr4: Milstein, C. 1967. Nature (Lo11do11) 216:330.
`X: Milstein, C. 1968. Biochem. J. 110:631.
`Bel, Man, B6: Milstein, C. 1968. Fed. Eur. Bioclzem. Soc. Symp. on -y-globuJi11, Prague.
`Day, MBJ46, Roy: Atlas of Protein Sequence and Structure, M. 0. Dayhoff, Editor. 1969.
`Mz: Milstein, C., B. Frangione, and J. R. L. Pink. 1967. Cold Spring Harbor Symp. Quant.
`Biol. 32:31.
`Ale, Car, Dee: Milstein, C., C. P. Milstein, and A. Feinstein. 1969. Na,ure (Lo1tdon) 221:151.
`Cra, Pap, Lux, Mon, Con, Tra, Nig, Win, Gra, Cas, Smi: Niall, H., and P. Edman. 1967.
`Natt're (Londo11) 216:262.
`MOPC 149, AdjPC 9, MOPC 157: Perham, R., E. Appella, and M. Potter. 1%6. Science
`(Washington) 154:391.
`Kern: Ponstingl, H., M. Hess, and N. Hilschmann. 1968. Hoppe-Seyler's Z. P!tysiol. Clzem.
`349:867.
`Tew: Putnam, F. W. 1969. Science (Washington). 163:633.
`Ag, Ha, :Bo, Sh: Putnam, F. W., K. Titani, M. Wilder, and T. Shinoda. 1967. Cold Spring
`JJa;rbor Symp. Quant. Biel. 32:9; Titani, K., T. Shinoda, and F. W. Putnam. 1969. J.
`Biol. Chem. 244:3550.
`Tl: Suter, L., H. U. Barnikol, S. Watanabe, and N. Hilscbmann. 1969. Hoppe-Seyler's Z.
`Physiol. Chem. 360:275.
`
`The accumulation of such large numbers of sequences makes it possible to use
`statistical criteria in defining the types of residues. Thus in earlier studies,
`an invariant residue was rigidly defined, e.g., a position at which all samples
`showed the same amino acid residue sometimes allowing a single exception.
`The definition of an invariant residue used in this paper is taken as a position
`at which 88-90% or more of the samples contain the same amino acid. This
`may allow potential functions to be recognized despite possible errors or
`uncertainties in sequence, or occasional substitutions compatible with function.
`A summary of the sequence data is provided in Table I which lists the amino
`acids found at any position in any subgroup of human K-, hwnan "A-, and mouse
`K-chains, the number of times each occurs, and the total number of sequences
`
`5 of 40
`
`BI Exhibit 1053
`
`
`
`216
`
`BENCE JONES PROTEINS Ai'lD MYELOMA LIGHT CHAINS
`
`TABLE I
`A111ino Acids Fo11n4 at each Position in the Variable Region of the Various S11bg101tps of Hmnan
`K-, Buman A- and 1ltlouse K-Bence Jones Proteins
`
`No. of
`Position Protein Amino
`Sequences Acids
`Studied
`
`Total Human Kappa Human Lambda
`I II I!I
`I II !II DI v
`
`Mouse Kappa
`I II
`
`0
`
`l
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`74
`
`?4
`
`7 3
`
`72
`
`71
`
`70
`
`69
`
`63
`
`Glu
`
`'f.urs
`PCA
`Asp
`Asx
`Glu
`Glx
`
`l
`73
`
`1
`17
`29
`5
`15
`l
`6
`
`Ile lits
`4
`'ryr
`l
`Val
`1
`Met
`Ser
`19
`
`Ile
`Pro
`Leu
`Val
`Ala
`Asp
`Glu
`Gl.n
`Glx
`
`1
`l
`l
`33
`9
`1
`2
`21
`3
`
`43
`Leu
`2
`Val
`Met 26
`
`Ala
`2
`Th.r &r
`Ser
`l
`
`Gln
`Glx
`
`Pro
`Tbr
`Ser
`Asp
`
`63
`6
`
`20
`l
`41
`l
`
`0 l 0
`23 3 17
`
`0 0 l
`0 0 0
`18 4 l
`5 0 0
`0 0 14
`0 0 l
`0 0 0
`
`22 3 J.6
`0 0 0
`]_ 0 0
`0 0 1
`0 0 0
`
`0 0 1
`0 0 0
`l 0 0
`0 3 16
`0 0 0
`0 0 0
`0 0 0
`19 0 0
`3 0 0
`
`3 ]_ l�
`0 0 1
`20 2 2
`
`0 0 0
`23 3 17
`0 0 0
`
`20 3 16
`3 0 l
`
`0 0 0
`0 1 0
`22 2 14
`0 0 0
`
`0 0 0
`9 2 6
`
`0 0
`4 2
`
`0 0 0 0 0
`8 2 6
`0 0
`0 0 0
`0 0
`0 0 0
`0 0
`l 0 0
`0 0
`0 0 0
`0 0
`4 2
`0 0 0
`
`0 0 0 0 0
`0 0 0
`4 0
`0 0 0
`0 0
`0 0 0 0 0
`0 2
`9 2 6
`
`0 0 0 0 0
`0 0 1
`0 0
`0 0 0 0 0
`8 0 0
`1 0
`l 2 5
`l 0
`]_ 0
`0 0 0
`1 1
`0 0 0
`0 0
`0 0 0
`0 0 0 0 0
`
`9 2 6
`0 0 0
`0 0 0
`
`0 0 2
`9 2 3
`0 0 1
`
`8 l 6
`l l 0
`
`4 l
`0 0
`0 0
`
`0 0
`4 1
`0 0
`
`4 l
`0 0
`
`3 0
`9 2 6
`0 0 0
`0 0
`0 0 0 0 0
`0 1
`0 0 0
`
`0
`2
`
`0
`0
`2
`0
`0
`0
`0
`
`2
`0
`0
`0
`0
`
`0
`5
`
`0
`]_
`If
`0
`0
`0
`0
`
`5
`0
`0
`0
`0
`
`0
`0
`0
`0
`0 0
`5
`0
`0
`0
`0
`0
`0
`0
`2
`0
`0
`0
`
`0
`0
`2
`
`0
`2
`0
`
`l
`0
`
`0
`0
`1
`0
`
`3
`l
`0
`
`0
`3
`0
`
`3
`0
`
`0
`0
`2
`0
`
`6 of 40
`
`BI Exhibit 1053
`
`
`
`TAI TE WU AND ELVIN A. KABAT
`
`217
`
`TABLE I-Contint4ed
`
`No. of
`Amino Total Human Kappa
`Position Protein
`Sequences Acids
`I II III
`Studied
`
`Human Lambda Mouse Kappa
`I II III IV v
`I II
`
`8
`
`9
`
`64
`
`63
`
`10
`
`63
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`63
`
`61
`
`61
`
`61
`
`61
`
`61
`
`61
`
`Pro
`Ala
`
`Leu
`Ala
`Thr
`Ser
`Gly
`Asx
`
`�he
`Thr
`Ser
`
`Leu
`Val
`Ala
`
`Pro
`Ala
`Ser
`
`Leu
`Val
`Met
`Ala
`Gly
`
`58
`6
`
`3
`1
`l
`41
`10
`1
`
`l
`17
`25
`20
`
`43
`15
`5
`
`4
`1
`56
`
`12
`11
`1
`23
`14
`
`6
`Ala
`Thr
`9
`46
`Ser
`Pro 36
`4
`Leu
`Val
`20
`l
`Asx
`
`Arg
`Gly
`
`Asp
`Glu
`Gln
`Glx
`
`l
`60
`
`23
`17
`19
`2
`
`22 3 15
`0 0 0
`
`0 3 0
`0 0 4
`1 0 0
`21. 0 0
`0 0 10
`0 0 1
`
`1 0 0
`3 0 14
`18 4 0
`0 0 0
`
`22 4 14
`0 0 0
`0 0 0
`
`0 4 0
`0 0 0
`21 0 13
`
`0 0 l2
`2 4 0
`0 0 l
`19 0 0
`0 0 0
`
`0 0 0
`0 4 0
`21 0 13
`
`0 4 13
`l 0 0
`20 0 0
`0 0 0
`
`1 0 0
`20 4 13
`
`21 0 l
`0 4 11
`0 0 0
`0 0 1
`
`9 2 0
`0 0 6
`
`0 0 0
`0 0 0
`0 0 0
`9 2 6
`0 0 0
`0 0 0
`
`0 0 0
`0 0 0
`0 0 0
`9 2 6
`0 0 0
`6 0 6
`3 2 0
`
`0 0 0
`0 0 0
`9 2 6
`
`0 0 0
`0 0 0
`0 0 0
`3 0 0
`6 2 6
`
`5 0 0
`4 0 0
`0 2 6
`
`8 2 6
`0 0 0
`0 0 0
`1 0 0
`
`0 0 0
`9 2 6
`0 0 0
`0 0 l
`8 2 5
`l 0 0
`
`3 l
`0 0
`
`0 0
`0 1.
`0 0
`2 0
`0 0
`0 0
`
`0 0
`0 0
`0 0
`2 1
`
`0 0
`2 1
`0 0
`
`0 0
`0 0
`2 l
`
`0 0
`2 l
`0 0
`0 0
`0 0
`
`0 1
`0 0
`2 0
`
`2 0
`0 1
`0 0
`0 0
`
`0 0
`2 l
`
`0 0
`0 0
`2 l
`0 0
`
`l
`0
`
`0
`0
`0
`l
`0
`0
`
`0
`0
`l
`0
`
`1
`0
`0
`
`0
`0
`1
`
`0
`0
`0
`l
`0
`
`0
`c
`l
`
`0
`l
`0
`0
`
`0
`l
`
`0
`l
`0
`0
`
`2
`0
`
`0
`2
`0
`0
`0
`0
`
`0
`0
`2
`0
`
`2
`0
`0
`
`0
`l
`l
`
`0
`2
`0
`0
`0
`
`0
`l
`1
`
`l
`l
`0
`0
`
`0
`2
`
`l
`0
`1
`0
`
`7 of 40
`
`BI Exhibit 1053
`
`
`
`218
`
`BENCE JONES PROTEINS AND MYELOJl{A LIGHT CIIAINS
`
`TABLE I-Contimied
`
`No. of
`position Protein Amino Total Human Kallpa
`Sequences Acids
`I II III
`Studies
`
`Huma.n .Lambda.
`I II III IV v
`
`t·buse Kappa
`I II
`
`18
`
`61
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`53
`
`53
`
`li3
`
`42
`
`30
`
`26
`
`25
`
`21!
`
`Pro
`Lys
`A.la
`Arg
`'l'hr
`Ser
`Gly
`
`I�
`l
`1
`4o
`5
`9
`l
`
`Ile
`7
`Val
`28
`Ala 1.8
`l
`Ile
`l
`Val
`3
`A.la
`Arg
`l
`Tbr 4o
`Ser
`7
`30
`12
`l
`l
`19
`22
`
`Ile
`L'?u
`Va.l
`Ala
`Thr
`Ser
`
`Cys
`
`Arg
`Thr
`Ser
`Gly
`Cln
`Clx
`
`Ala
`Ser
`CiY
`
`Thx·
`Ser
`Gly
`A.sp
`
`30
`11
`2
`6
`l
`4
`2
`
`13
`2
`10
`
`2
`16
`2
`4
`
`0 4 0
`0 0 0
`0 0 0
`21 0 13
`0 0 0
`0 0 0
`0 0 0
`
`l 0 0
`17 0 0
`0 4 10
`0 0 0
`0 0 0
`l 0 2
`0 0 0
`17 0 8
`0 4 0
`14 4 0
`l 0 9
`0 0 1
`l 0 0
`14 0 0
`Ji 9
`0
`
`9 3 4
`l 3
`0 0 0
`0 0 0
`0 0 0
`3 0 0
`2 0 0
`6 0 4
`0 2 0
`0 0 0
`0 0 0
`6 2 4
`0 0 0
`0 0 0
`
`0 0 0 0 0
`l 0 0
`0 0
`0 0
`1 0 0
`4 0 0
`0 0
`2 1
`1 0 1
`0 0
`1 2 5
`1 0 0 0 0
`0 0 6
`0 0
`6 2 0 0 1
`2 0
`l 0 0
`l 0 0 0 0
`l 0
`0 0 0
`0 0
`0 0 0
`0 0 0 0 l
`6 2 6
`0 0
`l 0
`0 0 0
`3 l
`5 2 0
`0 0
`0 0 0
`0 0
`0 0 0
`0 0 0 0 0
`3 1
`0 0 0
`0 0
`5 2 0
`3 1
`5 2 0
`0 0 0 0 0
`0 0
`0 2 0
`2 0
`4 0 0
`0 0 0 l 0
`0 l
`0 0 0
`0 0
`0 0 0
`0 0
`0 0
`3 1
`0 0
`0 0
`0 0
`3 1
`
`0 0 0
`0 0 0
`4 2 0
`0 2 0
`1 0 0
`2 0 0
`0 0 0
`
`0 0
`0
`0
`0 0
`l
`l
`0 0
`0 1
`0
`0
`
`0
`0
`l
`l
`l
`0
`0 0
`0
`0
`0
`0
`0
`0
`1
`0
`l
`1
`
`l
`0
`1
`1
`0 0
`0
`0
`0
`l
`2
`0
`
`2
`
`1
`2
`l
`0
`0
`0
`0
`0 0
`0
`0
`0
`0
`2
`0
`0
`
`1
`0
`0
`
`0 0
`2
`1
`0
`0
`0
`0
`
`8 of 40
`
`BI Exhibit 1053
`
`
`
`TAI TE WU AND ELVIN A. KABAT
`
`219
`
`TABLE I-Continued
`
`Position
`
`No. of
`Protein
`Alllino
`Sequences Acids
`Studied
`
`Total Human Kappa Human Lambda Mouse Kappa
`I II III
`I II III IV v
`I II
`
`Z{
`
`23
`
`a
`
`b
`
`c
`
`d
`
`e
`
`f
`
`22
`
`22
`
`22
`
`22
`
`22
`
`22
`
`28
`
`22
`
`Iqs
`Ser
`Asn
`Glu
`Gln
`Glx
`
`Ser
`Asn
`
`Leu
`Val
`
`Leu
`
`Thr
`Ser
`Asp
`
`Asp
`Asn
`ASX.
`
`Val
`Ser
`Gcy
`Glx.
`
`Ile
`Leu
`Val
`Met
`Thr
`Ser
`Gly
`His
`Asp
`Asx
`
`1
`5
`1
`1
`13
`2
`
`5
`1
`16
`
`2
`1
`19
`
`2
`20
`
`l
`3
`l
`17
`
`2
`3
`1
`16
`
`2
`2
`l
`l
`16
`
`l
`4
`2
`1
`1
`3
`2
`l
`4
`3
`
`0 0 0
`0 0 0
`0 0 0
`0 0 0
`5 1 4
`1 1 0
`
`0 1 3
`0 l 0
`6 0 1
`
`0 2 0
`0 0 0
`6 0 4
`
`0 2 0
`6 0 4
`
`0 0 0
`0 0 0
`0 1 0
`6 l 4
`
`0 1 0
`0 0 0
`0 0 0
`6 1 4
`0 0 l
`0 l 0
`0 0 0
`0 1 0
`6 0 3
`
`0 0 0
`0 0 1
`0 0 2
`0 0 0
`0 0 0
`l l 1
`0 l 0
`0 0 0
`4 0 0
`1 0 0
`
`l 0
`0 0 0
`3 1 0 0 1
`1 0
`0 0 0
`0 0 0
`l 0
`0 0 0 0 0
`0 0 0 0 0
`
`0 0 0 0 0
`0 0 0
`0 0
`3 l 0
`2 l
`
`0 0 0
`0 0 0
`3 1 0
`
`0 0
`0 0
`2 l
`
`0 0 0 0 0
`2 l
`3 l 0
`
`1 0 0 0 0
`2 1 0 0 0
`0 0 0
`0 0
`0 0 0
`2 l
`
`0 1 0
`3 0 0
`0 0 0
`0 0 0
`
`0 0
`0 0
`0 0
`2 l
`
`0 1 0 0 0
`0 0 0
`0 0
`l 0 0
`0 0
`0 0 0
`0 0
`2 1
`2 0 0
`
`l 0 0 0 0
`0 0 0
`2 1
`0 0 0 0 0
`l 0 0 0 0
`l 0 0
`0 0
`0 0 0
`0 0
`0 l 0
`0 0
`0 0 0
`0 0
`0 0 0
`0 0
`0 0 0 0 0
`
`0
`0
`0
`0
`0
`0
`0 0
`2
`1
`0 0
`
`1
`0
`0 0
`1
`l
`
`0
`0
`l
`
`0
`l
`1
`
`0 0
`l
`2
`
`0
`0
`0
`l
`
`0
`0
`0
`l
`
`0
`0
`0
`2
`
`0
`0
`1
`l
`
`0
`0
`l
`0
`0 0
`0 0
`l
`1
`
`0 0
`0
`0
`0
`0
`0 0
`0 0
`0 0
`0 0
`l
`0
`0 0
`1
`l
`
`9 of 40
`
`BI Exhibit 1053
`
`
`
`220
`
`BENCE JONES PROTEINS AND MYEWMA LIGHT CHAINS
`
`TABLE I-Contim1ed
`
`Position
`
`No. of
`Protein Amino
`Sequences Acids
`Studied
`
`Total Human Kappa
`I II III
`
`Htunan Lambda
`I II III IV v
`
`Mouse Kappa
`I II
`
`29
`
`21
`
`30
`
`21
`
`31
`
`20
`
`32
`
`20
`
`33
`
`18
`
`34
`
`18
`
`Ile
`Arg
`Ser
`Gly
`Glu
`Asp
`Asx
`
`!le
`Iqs
`Ser
`Gly
`Asp
`Asn
`Asx
`
`Tyr
`Phe
`Iqs
`Thr
`Ser
`His
`Asn
`Asx
`
`Trp
`Tyr
`Phe
`Leu
`Thr
`Asp
`Asn
`
`8
`2
`3
`4
`l
`1
`2
`
`2
`2
`2
`5
`1
`8
`l
`
`l
`l
`2
`2
`7
`1
`4
`2
`
`l
`10
`5
`l
`l
`1
`1
`
`Leu ll
`4
`Val
`Met
`1
`l
`Ala
`l
`Ser
`
`Tyr
`Ala
`Ser
`Asp
`Asn
`Asx
`
`l
`6
`3
`l
`4
`3
`
`6 0 0
`0 0 l
`0 0 3
`0 0 0
`0 0 0
`0 l 0
`0 l 0
`
`l 0 0
`1 0 0
`1 0 0
`0 2 1
`0 0 0
`3 0 3
`0 0 0
`
`0 0 0
`0 0 0
`l 0 0
`1 1 0
`l 0 2
`l 0 0
`l 0 2
`l 1 0
`
`l 0 0
`2 2 3
`3 0 1
`0 0 0
`0 0 0
`0 0 0
`0 0 0
`
`4 2 4
`0 0 0
`0 0 0
`0 0 0
`0 0 0
`
`0 0 0
`1 0 4
`0 0 0
`0 l 0
`2 l 0
`l 0 0
`
`0 0 0 0 0
`0 0 0 0 1
`0 0
`0 0 0
`l 0
`2 0 0
`0 0 0
`l 0
`0 0 0 0 0
`0 l 0
`0 0
`
`0 0 0 0 0
`1 0
`0 0 0
`0 0 0 0 0
`0 0 0 0 1
`l 0
`0 0 0
`2 0 0 0 0
`0 0
`0 l 0
`
`0 0 0 0 l
`l 0
`0 0 0
`0 0
`0 1 0
`0 0 0 0 0
`2 0 0
`0 0
`0 0 0 0 0
`0 0
`0 0 0
`0 0 0
`0 0
`
`0 0
`0 0 0
`2 l 0 0 0
`0 0 0 0 0
`0 0 0
`0 0
`l 0
`0 0 0
`0 0 0 0 1
`0 0 0 0 0
`
`0 0 0 0 0
`1 0
`2 1 0
`0 0 0 0 0
`0 0 0
`0 1
`0 0 0 0 0
`
`l 0 0
`0 0
`0 1
`0 0 0
`l 0
`1 ! 0
`0 0
`0 0 0
`0 0 0 0 0
`0 0 0 0 0
`
`1
`l
`0
`0
`0 0
`1
`0
`0
`0
`0 0
`0
`0
`
`0 1
`0
`0
`l.
`0
`0
`l
`0 0
`0
`0
`0
`0
`
`0
`0
`0 0
`0 0
`0 0
`1
`l
`0 0
`l
`0
`0 0
`
`0
`0
`0
`0
`l
`0
`l 0
`0 0
`0
`0
`l
`0
`
`1
`0
`0 0
`l
`0
`0
`0
`1
`0
`
`0 0
`0
`0
`0 0
`0
`0
`1
`0
`l
`l
`
`10 of 40
`
`BI Exhibit 1053
`
`
`
`TAI T£ WU AND ELVIN A. KABAT
`
`221
`
`TABLE I-Continued
`
`Position
`
`No. of
`Protein Al!lino
`Sequences Acids
`Studied
`
`Total Human Kappa
`I II III
`
`Ruman Lambda Mouse Kappa.
`I II III IV v
`I II
`
`35
`"!P
`
`4o
`
`41
`
`42
`
`17
`
`17
`
`16
`
`16
`
`16
`
`1.6
`
`16
`
`1.6
`
`43
`
`16
`
`44
`
`45
`
`1.6
`
`16
`
`rrp
`
`Tyr
`Phe
`Leu
`His
`
`Leu
`Gln
`Glx
`
`His
`Gln
`Glx
`
`Leu
`Lys
`Arg
`Gly
`His
`Asx
`
`Pro
`Al.a
`
`I.vs
`Gly
`
`I.Ys
`Arg
`Tllr
`Gln
`Glx
`
`Pro
`Ala
`Thr
`Ser
`Gl.n
`
`Ile
`Pro
`
`Leu
`lifs
`Arg
`Ser
`Glx
`
`17
`
`13
`2
`l
`l
`
`2
`12
`2
`
`l
`12
`3
`
`2
`9
`2
`l
`l
`l
`
`1.5
`l
`
`l
`15
`
`3
`l
`2
`7
`3
`
`1.
`ll
`l
`2
`l
`
`l
`15
`
`2
`9
`3
`1
`l
`
`4 2 4
`
`2 l 0
`
`l l
`
`4 2 4
`0 0 0
`0 0 0
`0 0 0
`
`0 2 0
`3 0 4
`0 0 0
`
`0 0 0
`3 l 4
`0 l 0
`
`0 0 0
`2 2 3
`0 0 l
`l 0 0
`0 0 0
`0 0 0
`
`1. 4
`3
`0 l 0
`
`l 0 0
`2 2 4
`
`3 0 0
`0 0 0
`0 0 0
`0 l 4
`0 l 0
`
`0 0 0
`3 0 4
`0 0 0
`0 l 0
`0 l 0
`
`0 0 0
`3 2 4
`
`0 0 0
`3 0 1.
`0 0 3
`0 l 0
`0 l 0
`
`l l 0 0 l
`0 0 0
`l 0
`0 0 0 0 0
`l 0 0 0 0
`
`0 0 0 0 0
`2 l 0
`l l
`0 0 0 0 0
`
`l 0 0 0 0
`l 1.
`l l 0
`0 0 0 0 0
`
`2 0 0 0 0
`0 0 0 0 l
`1. 0
`0 0 0
`0 0 0 0 0
`0 l 0 0 0
`0 0 0 0 0
`
`l l
`2 1. 0
`0 0 0 0 0
`
`0 0 0 0 0
`1. l
`2 1. 0
`
`0 0 0 0 0
`0 l 0 0 0
`2 0 0 0 0
`l l
`0 0 0
`0 0 0 0 0
`
`0 0 0 0 0
`2 l. 0 0 l
`0 0 0 0 0
`l 0
`0 0 0
`0 0 0 0 0
`
`0 0 0 0 0
`l l
`2 l 0
`
`l l
`0 0 0
`2 1. 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`
`l
`
`l
`
`0 0
`0
`l
`l 0
`0 0
`
`0 0
`0 0
`l
`l
`
`0 0
`0 0
`1.
`l
`
`0 0
`l
`0
`0 0
`0 0
`0 0
`l 0
`
`l
`l
`0 0
`
`0 0
`l
`l
`
`0 0
`0 0
`0 0
`0 0
`l
`l
`
`l.
`0
`0 0
`l 0
`0 0
`0 0
`
`l 0
`l
`0
`
`0 0
`l
`l
`0 0
`0 0
`0 0
`
`11 of 40
`
`BI Exhibit 1053
`
`
`
`222
`
`BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS
`
`TABLE I-Continued
`
`No. of
`Position Protein .Amino Total Rwnan Kappa Human Lambda Mouse Kappa
`I II III IV v
`I n
`Sequences Acids
`I II III
`Studied
`
`46
`
`If{
`
`li8
`
`49
`
`50
`
`14
`
`14
`
`14
`
`14
`
`lli
`
`51
`
`14
`
`52
`
`14
`
`53
`
`14
`
`54
`
`111
`
`Ile
`:reu
`Arg
`
`Leu
`Va.l
`
`Ile
`Met
`
`fyr
`Phe
`
`Leu
`Val
`Lys
`Ala
`Arg
`Tbr
`Ser
`Gly
`Asp
`Clu
`
`Leu
`Val
`Ala
`Arg
`Thr
`Gly
`His
`Asp
`
`Ser
`Asp
`Asn
`Glu
`
`Tyr
`Lys
`Ser
`Asn
`Glu
`Glx
`
`Leu
`Arg
`Gln
`
`1
`12
`l
`
`ll
`? .)
`
`12
`2
`
`13
`l
`
`1
`l
`l
`2
`1
`l
`l
`3
`�
`1
`
`1
`2
`5
`1
`l
`1
`1
`2
`
`10
`l
`2
`1
`
`1
`3
`4
`4
`l
`1
`
`4
`9
`l
`
`1 0 0
`2 2 2
`0 0 0
`
`3 2 2
`0 0 0
`
`2 2 1
`1 0 1
`
`3 2 2
`0 0 0
`
`0 l 0
`0 0 1
`1 0 0
`0 0 0
`0 0 0
`0 1 0
`0 0 0
`0 0 1
`� 0 0
`0 0 0
`
`0 1 0
`0 0 l
`3 0 l
`0 0 0
`0 0 0
`0 1 0
`0 0 0
`0 0 0
`
`3 2 2
`0 0 0
`0 0 0
`0 0 0
`
`0 1 0
`l 0 0
`1 0 2
`1 1 0
`0 0 0
`0 0 0
`
`3 0 0
`0 2 2
`0 0 0
`
`0 0 0
`2 l 0
`0 0 0
`
`2 0 0
`0 1 0
`
`2 1 0
`0 0 0
`
`2 0 0
`0 l 0
`
`0 0 0
`0 0 0
`0 0 0
`0 0 0
`1 0 0
`0 0 0
`0 0 0
`0 1 0
`0 0 0
`1 0 0
`
`0 0 0
`0 1 0
`0 0 0
`0 0 0
`0 0 0
`0 0 0
`0 0 0
`2 0 0
`
`0 l 0
`l 0 0
`1 0 0
`0 0 0
`
`0 0 0
`2 0 0
`0 0 0
`0 0 0
`0 1 0
`0 0 0
`
`0 0 0
`2 1 0
`0 0 0
`
`0 0
`l l
`0 0
`
`0 0
`l 1
`
`1 1
`0 0
`
`1 1
`0 0
`
`0 0
`0 0
`0 0
`0 0
`0 0
`0 0
`1 0
`0 1
`0 0
`0 0
`
`0 0
`0 0
`0 0
`0 1
`0 0
`0 0
`1 0
`0 0
`
`0 0
`0 0
`0 1
`1 0
`
`0 0
`0 0
`0 0
`0 1
`0 0
`1 0
`
`0 0
`1 l
`0 0
`
`0
`0
`1
`
`1
`0
`
`1
`0
`
`l
`0
`
`0
`0
`0
`1
`0
`0
`0
`0
`0
`0
`
`0
`0
`0
`0
`1
`0
`0
`0
`
`l
`0
`0
`0
`
`0
`0
`1
`0
`0
`0
`
`1
`0
`0
`
`0
`l
`0
`
`1
`0
`
`1
`0
`
`1
`0
`
`0
`0
`0
`1
`0
`0
`0
`0
`0
`0
`
`0
`0
`1
`0
`0
`0
`0
`0
`
`l
`0
`0
`0
`
`0
`0
`0
`l
`0
`0
`
`0
`0
`1
`
`12 of 40
`
`BI Exhibit 1053
`
`
`
`TAI TE WU AND ELVIN A. KABAT
`
`223
`
`TABLE I-Continued
`
`No. of
`Position Protein Amino Total Human J<a.ppe.
`I II III
`Sequences Acids
`Studied
`
`Huroan Lambda
`I II III J:V v
`
`Mouse Kappa.
`I II
`
`55
`
`16
`
`16
`
`16
`
`16
`
`16
`
`16
`
`56
`
`57
`
`58
`
`59
`
`60
`
`61
`
`Pro
`Al.a.
`Gly
`Asx
`Glu
`
`Ala
`Thr
`Ser
`
`Thr
`Gly
`
`Ile
`Va.l
`Thr
`
`5
`6
`l
`l
`3
`
`l
`5
`10
`
`1
`15
`
`6
`9
`l
`
`Pro
`
`16
`
`Va.l
`lu's
`Ala
`Ser
`Asp
`Asn
`Glu
`
`1
`l
`1
`3
`8
`l
`l
`
`0 0 0
`0 2 4
`0 0 0
`0 0 0
`3 0 0
`
`1. 0 0
`l 0 4
`1. 2 0
`
`0 0 0
`3 2 4
`
`0 0 3
`3 2 0
`0 0 1
`
`3 2 4
`
`0 0 l
`0 c 0
`0 0 0
`3 0 0
`0 1. 3
`0 1 0
`0 0 0
`
`2 l 0
`0 0 0
`0 0 0
`0 0 0
`0 0 0
`
`1. l
`0 0
`0 0
`0 0
`0 0
`
`0 0 0 0 0
`0 0 0 0 0
`1 1.
`2 1 0
`
`0 0 0
`l 0
`2 1 0 0 l
`
`l 0 0
`l 1
`1 1. 0 0 0
`0 0 0 0 0
`
`2 1 0
`
`l l
`
`0 0 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`0 l
`2 l 0
`0 0 0 0 0
`1. 0
`0 0 0
`
`0 0
`0 0
`l
`0
`1
`0
`0
`0
`
`0 0
`0
`0
`1
`1.
`
`0
`l
`
`0
`l
`0
`
`l
`
`0
`l
`
`0
`l
`0
`
`l
`
`0 0
`0
`1
`0
`1
`0 0
`0 0
`0
`0
`0 0
`
`62
`
`63
`
`64
`
`65
`
`66
`
`67
`
`16
`
`16
`
`16
`
`16
`
`16
`
`16
`
`16
`
`A:rg
`
`Ile
`Phe
`
`Ile
`Ser
`
`Ala.
`Gly
`
`Thr
`Ser
`
`lu's
`Arg
`Ser
`GJ.;y
`
`Phe
`Ser
`
`16
`
`l
`15
`
`l
`1.5
`
`1
`15
`
`l
`15
`
`3
`1
`2
`10
`
`l
`15
`
`3 2 4
`
`2 1 0
`
`l l
`
`l
`
`l
`
`0 0 0
`3 2 4
`
`1 0 0
`2 2 4
`
`0 0 0
`3 2 4
`
`l 0 0
`2 2 4
`
`0 0 0
`0 0 0
`0 0 0
`3 2 4
`
`l 0 0
`2 2 4
`
`1 0 0 0 0
`l 1 0
`l 1
`
`0 0 0 0 0
`l 1
`2 1 0
`
`l 0 0 0 0
`l l 0
`l. l
`
`0 0 0 0 0
`2 l 0
`l l
`
`2 l 0 0 0
`0 0 0 0 0
`l ].
`0 0 0
`0 0 0 0 0
`
`0 0 0 0 0
`2 l 0
`l 1
`
`0 0
`1
`l
`
`0
`0
`l 1.
`
`0
`l
`
`0
`l
`
`0
`l
`
`0
`l
`
`0
`0
`].
`0
`0
`0
`0 l
`
`0
`l
`
`0
`1
`
`13 of 40
`
`BI Exhibit 1053
`
`
`
`224
`
`BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS
`
`TAB LE I-Co·1iti11uei
`
`Position
`
`No. of
`.Protein Amino Total Human Kappa Hwnan Lambda Mouse Kappe.
`I II
`I II III IV v
`Sequences Acids
`I II III
`Studied
`
`68
`
`69
`
`16
`
`16
`
`70
`
`16
`
`71
`
`16
`
`72
`
`73
`
`74
`
`75
`
`76
`
`77
`
`16
`
`16
`
`16
`
`16
`
`16
`
`17
`
`78
`
`17
`
`Gly 15
`l
`Asn
`
`3 2 4
`0 0 0
`
`2 0 0 l 1
`0 l 0 0 0
`
`Ala
`Thr
`Se1
`His
`Asp
`
`Thr
`Ser
`Asp
`Asx
`Glu
`
`'fyr
`Pbe
`Ala
`
`Thr
`Ser
`
`Phe
`Leu
`
`I.ys
`Ala
`Thr
`Gly
`Asn
`
`2
`11
`1
`l
`l
`
`3
`2
`9
`1
`l
`
`1
`10
`5
`
`11
`5
`
`2
`14
`
`1
`1
`12
`l
`l
`
`Ile 1.5
`1
`Val
`
`Tbr
`Ser
`His
`
`Pro
`Arg
`Ser
`Gly
`
`Leu
`Val
`Met
`Ala
`
`2
`13
`l
`
`l
`6
`4
`6
`
`13
`1
`1
`2
`
`0 0 1
`3 2 3
`0 0 0
`0 0 0
`0 0 0
`
`0 0 0
`0 0 0
`2 1 4
`0 1 0
`l 0 0
`
`0 0 0
`3 2 4
`0 0 0
`
`3 2 4
`0 0 0
`
`0 0 0 l 0
`2 0 0 0 0
`0 0 0 0 0
`0 0 0 0 l
`0 1 0 0 0
`
`0 l 0 l l
`2 0 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`
`0 0 0 0 0
`0 0 0 0 0
`2 l 0 l 1
`
`l 0 0 l 0
`l l 0 0 1
`
`2 0 0
`1 2 4
`
`0 0 0 0 0
`1 1
`2 1 0
`
`0 1 0
`0 0 0
`3 l 4
`0 0 0
`0 0 0
`
`3 2 4
`0 0 0
`
`0 0 0
`3 2 4
`0 0 0
`
`0 0 0
`0 2 4
`3 0 0
`l 0 0
`
`4 l. 4
`0 l 0
`0 0 0
`0 0 0
`
`0 0 0 0 0
`l 0 0 0 0
`0 1 0 l l
`1 0 0 0 0
`0 0 0 0 0
`
`l 1
`2 0 0
`0 1 0 0 0
`
`1 0 0 0 l
`l 1 0
`1 0
`0 0 0 0 0
`
`0 0 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`2 1 0 l l
`
`2 1 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`0 0 0 l 1
`
`l
`l
`0 0
`
`0 0
`0 l
`1
`0
`0 0
`0 0
`
`0 0
`0 0
`l
`1
`0 0
`0 0
`
`1 0
`0 l
`0 0
`
`0 0
`1
`l
`
`0 0
`1
`l
`
`0 0
`0 0
`1 0
`0 0
`0 1.
`
`l 1
`0 0
`
`0 0
`l 0
`0 1
`
`0 l
`0 0
`1 0
`0 0
`
`l 0
`0 0
`0 l
`0 0
`
`14 of 40
`
`BI Exhibit 1053
`
`
`
`TAI TE WU AND ELV1N A. KABAT
`
`225
`
`TABLE I-Continued
`
`No. of
`Position Protein Amino Total Human Kappa
`Sequences Acids
`I II III
`Studied
`
`Human Lambda
`I II Ill r.v v
`
`Mouse Kappa
`I II
`
`79
`
`8o
`
`17
`
`17
`
`81
`
`17
`
`82
`
`8:;
`
`84
`
`85
`
`86
`
`�
`
`17
`
`18
`
`18
`
`18
`
`20
`
`20
`
`8S
`
`21
`
`Arg
`Glu
`Gln
`Glx
`
`Pro
`Ala
`Thr
`Ser
`Glx
`
`Val
`Ala
`Gl.y
`Asp
`Asx
`Glu
`Glx
`Asp
`Asx
`
`Ile
`Phe
`Val
`Tbr
`Glu
`Glx
`
`Val
`Ala
`Cly
`
`Val
`Met
`·rhr
`His
`Asp
`Asx
`
`Tyr
`
`Tyr
`Phe
`His
`
`Cys
`
`3
`5
`6
`3
`
`9
`3
`l
`3
`l
`
`l
`1
`l
`l
`1
`10
`2
`14
`3
`
`2
`8
`l
`l
`5
`l
`
`l
`16
`1
`
`6
`l
`11
`1
`5
`1
`
`20
`
`16
`3
`l
`
`21
`
`0 c 0
`0 1 3
`4 0 0
`0 l l
`
`4 l 4
`0 l 0
`0 0 0
`0 0 0
`0 0 0
`
`0 0 0
`l 0 0
`0 0 0
`l 0 0
`0 0 0
`2 l 4
`0 l 0
`4 l 4
`0 l 0
`
`2 0 0
`2 1 4
`0 l 0
`0 0 0
`0 0 0
`0 0 0
`
`0 0 0
`l1
`4 l
`0 l 0
`
`0 2 4
`0 0 0
`4 0 0
`0 0 0
`0 0 0
`0 0 0
`
`2 l 0 0 0
`0 0 0 0 0
`l l
`0 0 0
`0 0 0 0 0
`
`0 0
`0 0 0
`0 l 0 0 l
`l 0 0 0 0
`l 0
`l 0 0
`0 0 0 0 0
`
`l 0
`0 0 0
`0 0
`0 0 0
`l 0 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`l 0 0 0 1
`0 l 0 0 0
`l 1
`2 0 0
`0 l 0
`0 0
`
`0 0
`0 0 0
`0 0
`0 0 0
`0 0
`0 0 0
`0 0 0 0 0
`2 l
`2 0 0
`0 l 0 0 0
`
`0 0 0 0 0
`2 1
`2 l 0
`0 0 0
`0 0
`
`0 0 0 0 0
`0 0 0 0 0
`0 0 0 0 0
`l 0 0 0 0
`2 l
`l 0 0
`0 l 0
`0 0
`
`6 2 4
`
`2 l 0
`
`2 l
`
`6 2 3
`0 0 l
`0 0 0
`
`2 l 0
`0 0 0
`l 0 0
`
`l l
`l 0
`0 0
`
`6 2 4
`
`3 l 0
`
`2 l
`
`0 0
`l 0
`0
`0
`l
`0
`
`0 0
`0 0
`0 0
`l 0
`1
`0
`
`0
`0
`0 0
`0 0
`0 0
`l
`0
`1 0
`0 0
`l 0
`l
`0
`
`0 0
`1 0
`0
`0
`l
`0
`0 0
`0
`0
`
`l 0
`1
`0
`0 0
`
`0
`0
`l
`0
`0
`0
`0 0
`1
`0
`0 0
`
`1
`
`l
`
`0 0
`l
`0
`0 0
`
`l
`
`l
`
`15 of 40
`
`BI Exhibit 1053
`
`
`
`226
`
`BENCE JONES PROTEINS A,'<D MYELOMA LIGHT CHAINS
`
`TABLE I-Contimwi
`
`No. of
`Position Protein Amino
`Sequence� Acids
`Studied
`
`Total
`
`Human Kappa Human Lambda
`I II lII IV v
`l Il IIl
`
`Mouse Kappa
`I II
`
`89
`
`22
`
`90
`
`22
`
`91
`
`22
`
`92
`
`21
`
`93
`
`21
`
`9�
`
`21
`
`Leu
`Met
`Ala
`Ser
`Asn
`can
`Glx
`
`Met
`Ala
`Thr
`Ser
`Gln
`Glx
`
`Trp
`Tyr
`Phe
`Ala
`Arg
`Ser
`
`Leu
`Val
`Lys
`Ala
`Cly
`Asp
`Asn
`Glu
`
`Tyr
`Thr
`Ser
`Cly
`His
`Asp
`Asn
`Asx
`Glu
`Gln
`
`Ile
`Leu
`Val
`Met
`Ala
`Arg
`Ser
`Asp
`Asx
`
`1
`l
`2
`1
`1
`15
`1
`
`1
`3
`2
`2
`13
`1
`
`5
`12
`l
`1
`2
`1
`
`2
`l
`l
`l
`3
`9
`l
`3
`
`l
`�
`7
`l
`1.
`1
`2
`l
`2
`l
`
`2
`5
`1
`l
`l
`l
`8
`1.
`l
`
`0 0 0
`0 l 0
`0 0 0
`0 0 0
`0 0 0
`6 2 4
`0 '.) 0
`
`0 1 0
`0 0 0
`0 0 0
`0 0 0
`6 2 lJ
`0 0 0
`
`0 0 0
`5 1 4
`1 0 0
`0 l 0
`0 l 0
`0 0 0
`
`0 2 0
`0 0 0
`0 0 0
`0