A matrix approach to human class II histocompatibility antigens: Reactions of four monoclonal antibodies with the products of nine haplotypes

Immunogenetics - Tập 19 - Trang 179-194 - 1984
Frances M. Brodsky1
1Becton Dickinson Monoclonal Center, Mountain View,

Tóm tắt

Three putative HLA-DC-specific monoclonal antibodies, Genox 3.53, BT3/4 and anti-Leu-10, and the HLA-DR-specific antibody, L243, were compared. Their interactions with molecules from homozygous cell lines expressing DR types 1 through 9 were studied. Indirect radioimmunoassays on 29 cell lines demonstrated that Genox 3.53 reactivity correlated with DR1, 2, 6; BT3/4 reactivity correlated with DR 1, 2, 4, 6, 8; and anti-Leu-10 reactivity correlated with DR1, 2, 4, 5, 6, 8, and 9. In addition, one of six DR3-positive cells and three DR7, DRw10-positive cells reacted with anti-Leu-10 and one of two DR9-positive cells reacted with BT3/4. Binding studies with soluble antigen and competitive radioimmunoassays demonstrated that all three antibodies reacted with the DC1 molecule. Preincubation with BT3/4 blocked anti-Leu-10 binding; Genox 3.53 and L243 did not. Genox 3.53 and L243 were only blocked by themselves. Serial immuno-precipitation showed anti-Leu-10 reacted with non-HLA-DR molecules from cells expressing DR types 1–6, 8 and 9. However, the molecules precipitated by anti-Leu-10 were characteristic class II major histocompatibility complex (MHC) molecules. Their α and β chains were of lower apparent molecular weight than the DR chains in all haplotypes. They also comigrated with the DC1 molecule precipitated by Genox 3.53. Serial immuno-precipitation also showed that anti-Leu-10 removed all Genox 3.53 reactive molecules from cell lysates, but Genox 3.53 removed only a subset of anti-Leu-10 reactive molecules. These studies show Genox 3.53, BT3/4, and anti-Leu-10 react exclusively with class II MHC molecules that are not HLA-DR, and most likely define different polymorphisms of DC molecules, the human equivalent of mouse I-A products.

Tài liệu tham khảo

Allison, J. P., Walker, L. E., Russell, W. A., Pellegrino, M. A., Ferrone, S., Reisfeld, R. A., Frelinger, J. A., and Silver, J.: Murine Ia and human DR antigens: homology of amino terminal sequences. Proc. Natl. Acad. Sci. U.S.A. 75: 3953–3956, 1978 Auffray, C., Kuo, J., De Mars, R., and Strominger, J. L.: A minimum of four human class II α-chain genes are encoded in the HLA region of chromosome 6. Nature 304: 174–177, 1983 Barnstable, C. J., Jones, E. A., and Bodmer, W. F.: Genetic structure of major histocompatibility regions. In E. S. Lennox (ed.): Defense and Recognition II A, Cellular Aspects, Volume 22, pp. 151–225, University Park Press, Baltimore, 1979 Benoist, C. O., Mathis, D. J., Kanter, M. R., Williams, V. E., and McDevitt, H. O.: The murine Iaα chains, Eα and Aα, show a surprising degree of sequence homology. Proc. Natl. Acad. Sci. U.S.A. 80: 534–538, 1983 Billing, R. and Lucero, K.: A monoclonal antibody against an epitope common to HLA-B locus antigens. Hum. Immunol. 4: 351–357, 1982 Bodmer, W. F., Batchelor, J. R., Bodmer, J. G., Festenstein, H., and Morris, P. J. (eds.): Histocompatibility Testing. 1977 Munksgaard, Copenhagen, 1977 Bono, M. R. and Strominger, J. L.: Direct evidence of homology between human DC-1 antigen and murine I-A molecules. Nature 299: 836–838, 1982 Brodsky, F. M., Bodmer, W. F., and Parham, P.: Characterization of a monoclonal anti β 2-microglobulin and its use in the genetic and biochemical analysis of major histocompatibility antigens. Eur. J. Immunol. 9: 536–545, 1979a Brodsky, F. M., Parham, P., Barnstable, C. J., Crumpton, M. J., and Bodmer, W. F.: Monoclonal antibodies for analysis of the HLA system. Immunol. Rev. 47: 3–61, 1979b Brodsky, F. M., Parham, P., and Bodmer, W. F.: Monoclonal antibodies to HLA-DRw determinants. Tissue Antigens 16: 30–48, 1980 Chen, Y. X., Evans, R., Pollack, M. S., Lanier, L. L., Phillips, J., Rousso, C., Warner, N. L., and Brodsky, F. M.: Characterization and expression of the HLA-DC antigens defined by anti-Leu 10. Hum. Immunol., in press, 1984 Corte, G., Calabi, F., Damiani, G., Bargellesi, A., Tosi, R., and Sorrentino, R.: Human Ia molecules carrying DCl determinants differ in both α and, β subunit from la molecules carrying DR determinants. Nature 292: 357–360, 1981 DeKretser, T. A., Crumpton, M. J., Bodmer, J. G., and Bodmer, W. F.: Two dimensional gel analysis of the polypeptides precipitated by a polymorphic HLA-DR1, 2, w6 monoclonal antibody: evidence for a third locus. Eur. J. Immunol. 12: 600–606, 1982 Duquesnoy, R. J. and Marrari, M.: MB Systems. In P. Terasaki (ed.): Histocompatibility Testing, 1980, pp. 552–555, Munksgaard, Copenhagen, 1980 Erlich, H. A., Stetler, D., Saiki, R., Gladstone, P., and Pious, D.: Mapping of the genes encoding the HLA-DR α chain and the HLA-related antigens to a chromosome 6 deletion using genomic blotting. Proc. Natl. Acad. Sci. U.S.A. 80: 2300–2304, 1983 Giles, R. C., Nunez, G., Hurley, C. K., Nunez-Roldan, A., Winchester, R., Stastny, P., and Capra, J. D.: Structural analysis of a human I-A homologue using a monoclonal antibody that recognizes an MB3-like specificity. J. Exp. Med. 157: 1461–1470, 1983 Goyert, S. M., Shively, J. E., and Silver, J.: Biochemical characterization of a second family of human la molecules, HLA-DS, equivalent to murine I-A subregion molecules. J. Exp. Med. 156: 550–566, 1982 Haynes, B. F., Reisner, E. G., Hemler, M. E., Strominger, J. L., and Eisenbarth, G. S.: Description of a monoclonal antibody defining an HLA allotypic determinant that includes specificities within the B5 cross-reacting group. Hum. Immunol. 4: 273–286, 1982 Holmes, N. J. and Parham, P.: Enhancement of monoclonal antibodies against HLA-A2 is due to antibody bivalency. J. Biol. Chem. 258: 1580–1586, 1983 Hurley, C. K., Shaw, S., Nadler, L., Schlossman, S., and Capra, J. D.: Alpha and beta chains of SB and DR antigens are structurally distinct. J. Exp. Med. 156: 1557–1562, 1982 Ivanyi, P.: Interspecies MHS relationships studied by serological and cellular cross-reactions. In R. A. Reisfeld and S. Ferrone (eds.): Current Trends in Histocompatibility, Volume I, pp. 133–182, Plenum Press, New York, 1980 Jensenius, J. C. and Williams, A. F.: The binding of anti-immunoglobulin to rat thymocytes and thoracic duct lymphocytes. Eur. J. Immunol. 4: 91–97, 1974 Karr, R. W., Kannapell, C. C., Stein, J. A., Gebel, A. M., Mann, D. L., Duquesnoy, R. J., Fuller, T. C., Rodey, G. E., and Schwartz, B. D.: Molecular relationships of the human B cell alloantigens, MT2, MB3, MT4 and DR5. J. Immunol. 128: 1809–1818, 1982 Kavathas, P., DeMars, R., Bach, F. H., and Shaw, S.: SB: a new HLA-linked human histocompatibility gene defined using HLA-mutant cell lines. Nature 293: 747–749, 1981 Kirchhausen, T., Harrison, S. C., Parham, P., and Brodsky, F. M.: Location and distribution of the light chains in clathrin trimers. Proc. Natl. Acad. Sci. U.S.A. 80: 2481–2485, 1983 Klein, J., Juretic, A., Baxevanis, C. N., and Nagy, Z. A.: The traditional and a new version of the mouse H2 complex. Nature 291: 455–460, 1981 Korman, A. J., Knudsen, P. J., Kaufman, J. F., and Strominger, J. L.: cDNA clones for the heavy chain of HLA-DR antigens obtained after immunopurification of polysomes by monoclonal antibody. Proc. Natl. Acad. Sci. U.S.A. 79: 1844–1848, 1982 Laemmli, U. K.: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685, 1970 Lampson, L. A. and Levy, R.: Two populations of la-like molecules on a human B cell line. J. Immunol. 125: 293–299, 1980 Lemonnier, F. A., Rebai, N., LeBouteiller, P. P., Malissen, B., Caillol, D. H., and Kourilsky, F. M.: Epitopic analysis of detergent-solubilized HLA molecules by solid-phase radioimmunoassay. J. Immunol. Methods 54: 9–22, 1982 Markert, M. L. and Cresswell, P.: Polymorphism of human B-cell alloantigens: Evidence for three loci within the HLA system. Proc. Natl. Acad. Sci. U.S.A. 77: 6101–6104, 1980 Minowada, J., Ohnuma, T., and Moore, G. E.: Rosette-forming human lymphoid cell lines. I. Establishment of evidence for origin of thymus-derived lymphocytes. J. Natl. Cancer Inst. 49: 891–895, 1972 Muller, C., Ziegler, A., Muller, G., Schunter, F., and Wernet, P.: Monoclonal antibody (Tu48) defining alloantigenic Class I determinants specific for HLA-Bw4 and HLA-Aw23, -Aw24 as well as -Aw32. Hum. Immunol. 5: 269–282, 1982 Murphy, D. B.: Serological cross-reactivity between the products of discrete Ia genes. Fed. Proc. 34: 1016, 1975 Nadler, L. M., Stashenko, P., Hardy, R., Pesando, J. M., Yunis, E. J., and Schlossman, S. F.: Monoclonal antibodies defining serologically distinct HLA-D/DR related Ia-like antigens in man. Hum. Immunol. 1: 77–90, 1981 Oi, V. T. and Herzenberg, L. A.: Localization of murine Ig-1b and Ig-1a (IgG2a) allotypic determinants detected with monoclonal antibodies. Mol. Immunol. 16: 1005–1017, 1979 Parham, P. and Brodsky, F. M.: Mouse monoclonal antibodies against HLA-A, B, C antigens. In G. J. Hämmerling, U. Hämmerling and J. F. Kearney (eds.): Monoclonal Antibodies and T Cell Hybridoms, pp. 67–76, Elsevier Publishing Co., Amsterdam, 1981 Parham, P. and Ploegh, H. L.: Molecular characterization of HLA-A, B homologues in owl monkeys and other nonhuman primates. Immunogenetics 11: 131–143, 1980 Parham, P., Androlewicz, M. J., Brodsky, F. M., Holmes, N. J., and Ways, J. P.: Monoclonal antibodies: purification, fragmentation, and application to structural and functional studies of class I MHC antigens. J. Immunol. Methods 53: 133–173, 1982 Parham, P., Kipps, T. J., Ward, F. E., and Herzenberg, L. A.: Isolation of heavy chain class switch variants of a monoclonal anti-DC1 hybridoma cell line: Effective conversion of non-cytotoxic IgG1 antibodies to cytotoxic IgG2 antibodies. Hum. Immunol. 8: 141–151, 1983 Quaranta, V., Tanigaki, N., and Ferrone, S.: Distribution of antigenic determinants recognized by three monoclonal antibodies (Q2/70, Q5/6 and Q5/13) on human la-like alloantigens and on their subunits. Immunogenetics 12: 175–182, 1981 Rebai, N., Malissen, B., Pierres, M., Accolla, R. S., Corte, G., and Mawas, C.: Distinct HLA-DR epitopes and distinct families of HLA-DR molecules defined by 15 monoclonal antibodies (MAb) either antiDR or allo-anti-lak cross-reacting with human DR molecule. I. Cross-inhibition studies of MAb cell surface fixation and differential binding of MAb to detergent-solubilized HLA molecules immobilized to a solid phase of first MAb. Eur. J. Immunol. 13: 106–111, 1983 Shackelford, D. A., Mann, D. L., van Rood, J. J., Ferrara, G. B., and Strominger, J. L.: Human B-cell alloantigens DC1, MT1 and LB 12 are identical to each other but distinct from the HLA-DR antigen. Proc. Natl. Acad. Sci. U.S.A. 78: 4566–4570, 1981 Shackelford, D. A., Kaufman, J. F., Korman, A. J., and Strominger, J. L.: HLA-DR antigens: Structure, separation of subpopulations, gene cloning and function. Immunol. Rev. 66: 133–187, 1982 Shaw, S., Johnson, A. H., and Shearer, G. M.: Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region that stimulate secondary allogeneic proliferative and cytotoxic responses. J. Exp. Med. 152: 566, 1980 Tanigaki, N. and Tosi, R.: The genetic control of human Ia alloantigens: A three-loci model derived from the immunochemical analysis of “supertypic” specificities. Immunol. Rev. 66: 5–38, 1982 Tanigaki, N., Tosi, R., Duquesnoy, R. J., and Ferrara, G. B.: Three Ia species with different structures and alloantigenic determinants in an HLA-homozygous cell line. J. Exp. Med. 157: 231–247, 1983 Thorsby, E. and Piazza, A.: Joint report from the sixth International Histocompatibility Workshop Conference II. Typing for HLA-D (LD-1 or MLC) determinants. In F. Kissmeyer-Nielson (ed.): Histocompatibility Testing, 1975, pp. 414–485, Munksgaard, Copenhagen, 1976 Trowsdale, J., Lee, J. S., Carey, J., Grosveld, F., Bodmer, J., and Bodmer, W. F.: Sequences related to HLA-DRα chain on human chromosome 6: Restriction enzyme polymorphism detected with DCa chain probes. Proc. Natl. Acad. Sci. U.S.A. 80: 1972–1976, 1983 Uhr, J. W., Capra, J. D., Vitetta, E. S., and Cook, R. G.: Organization of the immune response genes. Science 206: 292–297, 1979 Uotila, M., Ruoslahti, E., and Engvall, E.: Two-site sandwich enzyme immunoassay with monoclonal antibodies to human alpha-fetoprotein. J. Immunol. Methods 42: 11–15, 1981 van Leeuwen, A., Schuit, H. R. E., and van Rood, J. J.: Typing for MLC (LD): II. The selection of nonstimulator cells by MLC inhibition tests using SD-identical stimulator cells (MISIS) and fluorescence antibody studies. Transplant. Proc. 5: 1539–1542, 1973 Wake, C. T., Long, E. O., and Mach, B.: Allelic polymorphism and complexity of the genes for HLA-DR β-chains-direct analysis by DNA-DNA hybridization. Nature 300: 372–374, 1982 Williams, A. F.: Differentiation antigens of the lymphocyte cell surface. In R. R. Porter and G. L. Ada (eds.): Contemporary Topics in Molecular Immunology 6, pp. 83–116, Plenum Press, New York and London, 1977 Wiman, K., Larhammar, D., Claesson, L., Gustafsson, K., Shenning, L., Bill, P., Bohme, J., Denaro, M., Dobberstein, B., Hämmerling, U., Kvist, S., Servenius, B., Sundelin, J., Peterson, P. A., and Rask, L.: Isolation and identification of a cDNA clone corresponding to an HLA-DR antigen β chain. Proc. Natl. Acad. Sci. U.S.A. 79: 1703–1707, 1982