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. 1982 Jun;79(12):3813–3817. doi: 10.1073/pnas.79.12.3813

Structure of crossreactive human histocompatibility antigens HLA-A28 and HLA-A2: possible implications for the generation of HLA polymorphism.

J A López de Castro, J L Strominger, D M Strong, H T Orr
PMCID: PMC346518  PMID: 6179086

Abstract

The primary structure of two highly crossreactive human histocompatibility antigens, HLA-A28 and HLA-A2, has been determined to 96% and 90%, respectively, of the papain-solubilized molecules. Their sequences have been compared with the sequence of HLA-B7 and with each other in order to outline the sites of diversity. The overall homology between HLA-B7 and these HLA-A antigens is 86%. A large majority of the differences are located between residues 43 and 195. Within this area, substitutions cluster in at least three segments--residues 65-80, 105-116, and 177-194. HLA-A28 and HLA-A2 show 96% homology. Most of the differences fall within segments 65-74 and 107-116. These results strongly support the suggestion that residues in these segments are integral parts of the alloantigenic determinants of HLA-A28 and HLA-A2. It is further proposed that these three clusters may constitute major, albeit not exclusive, sites of antigenic diversity in human histocompatibility antigens. The nature of the differences among HLA-B7, HLA-A28, and HLA-A2 in the first variable segment suggests that gene conversion might play some role in the generation of HLA polymorphism.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baltimore D. Gene conversion: some implications for immunoglobulin genes. Cell. 1981 Jun;24(3):592–594. doi: 10.1016/0092-8674(81)90082-9. [DOI] [PubMed] [Google Scholar]
  2. Bodmer W. F. Evolutionary significance of the HL-A system. Nature. 1972 May 19;237(5351):139–passim. doi: 10.1038/237139a0. [DOI] [PubMed] [Google Scholar]
  3. Bragado R., López de Castro J. A., Juárez C., Albar J. P., García Pardo A., Ortí F., Vivanco-Martínez F. Chemical modification of carboxyl groups in human Fcgamma fragment --II. Location of acidic residues involved in complement activation. Mol Immunol. 1982 Apr;19(4):579–588. doi: 10.1016/0161-5890(82)90227-9. [DOI] [PubMed] [Google Scholar]
  4. Brodsky F. M., Parham P., Barnstable C. J., Crumpton M. J., Bodmer W. F. Monoclonal antibodies for analysis of the HLA system. Immunol Rev. 1979;47:3–61. doi: 10.1111/j.1600-065x.1979.tb00288.x. [DOI] [PubMed] [Google Scholar]
  5. Burnet F. M. A certain symmetry: histocompatibility antigens compared with immunocyte receptors. Nature. 1970 Apr 11;226(5241):123–126. doi: 10.1038/226123a0. [DOI] [PubMed] [Google Scholar]
  6. Coligan J. E., Kindt T. J., Uehara H., Martinko J., Nathenson S. G. Primary structure of a murine transplantation antigen. Nature. 1981 May 7;291(5810):35–39. doi: 10.1038/291035a0. [DOI] [PubMed] [Google Scholar]
  7. Cresswell P., Robb R. J., Turner M. J., Strominger J. L. Papain-solubilized HL-A antigens. Chromatographic and electrophoretic studies of the two subunits from different specificities. J Biol Chem. 1974 May 10;249(9):2828–2832. [PubMed] [Google Scholar]
  8. Cresswell P., Turner M. J., Strominger J. L. Papain-solubilized HL-A antigens from cultured human lymphocytes contain two peptide fragments. Proc Natl Acad Sci U S A. 1973 May;70(5):1603–1607. doi: 10.1073/pnas.70.5.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dickmeiss E., Soeberg B., Svejgaard A. Human cell-mediated cytotoxicity against modified target cells is restricted by HLA. Nature. 1977 Dec 8;270(5637):526–528. doi: 10.1038/270526a0. [DOI] [PubMed] [Google Scholar]
  10. Egel R. Intergenic conversion and reiterated genes. Nature. 1981 Mar 19;290(5803):191–192. doi: 10.1038/290191a0. [DOI] [PubMed] [Google Scholar]
  11. Evans G. A., Margulies D. H., Camerini-Otero R. D., Ozato K., Seidman J. G. Structure and expression of a mouse major histocompatibility antigen gene, H-2Ld. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1994–1998. doi: 10.1073/pnas.79.6.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Joysey V. C., Wolf E. HLA-A, -B and -C antigens, their serology and cross-reaction. Br Med Bull. 1978 Sep;34(3):217–222. doi: 10.1093/oxfordjournals.bmb.a071501. [DOI] [PubMed] [Google Scholar]
  13. Kimball E. S., Maloy W. L., Coligan J. E. Evidence for three carbohydrate prosthetic groups on mouse histocompatibility antigens H-2Kd and H-2Db. Mol Immunol. 1981 Jul;18(7):677–680. doi: 10.1016/0161-5890(81)90039-0. [DOI] [PubMed] [Google Scholar]
  14. Klapper D. G., Wilde C. E., 3rd, Capra J. D. Automated amino acid sequence of small peptides utilizing Polybrene. Anal Biochem. 1978 Mar;85(1):126–131. doi: 10.1016/0003-2697(78)90282-8. [DOI] [PubMed] [Google Scholar]
  15. Lai C. Y. Detection of peptides by fluorescence methods. Methods Enzymol. 1977;47:236–243. doi: 10.1016/0076-6879(77)47028-9. [DOI] [PubMed] [Google Scholar]
  16. López de Castro J. A., Orr H. T., Robb R. J., Kostyk T. G., Mann D. L., Strominger J. L. Complete amino acid sequence of a papain-solubilized human histocompatibility antigen HLA-B7. 1. Isolation and amino acid composition of fragments and of tryptic and chymotryptic peptides. Biochemistry. 1979 Dec 11;18(25):5704–5711. doi: 10.1021/bi00592a029. [DOI] [PubMed] [Google Scholar]
  17. Malissen M., Malissen B., Jordan B. R. Exon/intron organization and complete nucleotide sequence of an HLA gene. Proc Natl Acad Sci U S A. 1982 Feb;79(3):893–897. doi: 10.1073/pnas.79.3.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Martinko J. M., Halpern R., Adlersberg J. B., Nathenson S. G. Structure of murine major histocompatibility complex alloantigens: identification of cysteine residues involved in two intrachain disulfide bonds of H-2K. Mol Immunol. 1981 Oct;18(10):883–888. doi: 10.1016/0161-5890(81)90011-0. [DOI] [PubMed] [Google Scholar]
  19. McMichael A. J., Parham P., Rust N., Brodsky F. A monoclonal antibody that recognizes an antigenic determinant shared by HLA A2 and B17. Hum Immunol. 1980 Sep;1(2):121–129. doi: 10.1016/0198-8859(80)90099-3. [DOI] [PubMed] [Google Scholar]
  20. McMichael A. J., Ting A., Zweerink H. J., Askonas B. A. HLA restriction of cell-mediated lysis of influenza virus-infected human cells. Nature. 1977 Dec 8;270(5637):524–526. doi: 10.1038/270524a0. [DOI] [PubMed] [Google Scholar]
  21. Nairn R., Yamaga K., Nathenson S. G. Biochemistry of the gene products from murine MHC mutants. Annu Rev Genet. 1980;14:241–277. doi: 10.1146/annurev.ge.14.120180.001325. [DOI] [PubMed] [Google Scholar]
  22. Nakai N., Lai C. Y., Horecker B. L. Use of fluorescamine in the chromatographic analysis of peptides from proteins. Anal Biochem. 1974 Apr;58(2):563–570. doi: 10.1016/0003-2697(74)90225-5. [DOI] [PubMed] [Google Scholar]
  23. Nathenson S. G., Uehara H., Ewenstein B. M., Kindt T. J., Coligan J. E. Primary structural: analysis of the transplantation antigens of the murine H-2 major histocompatibility complex. Annu Rev Biochem. 1981;50:1025–1052. doi: 10.1146/annurev.bi.50.070181.005113. [DOI] [PubMed] [Google Scholar]
  24. Orr H. T., Lancet D., Robb R. J., Lopez de Castro J. A., Strominger J. L. The heavy chain of human histocompatibility antigen HLA-B7 contains an immunoglobulin-like region. Nature. 1979 Nov 15;282(5736):266–270. doi: 10.1038/282266a0. [DOI] [PubMed] [Google Scholar]
  25. Orr H. T., Lopez de Castro J. A., Parham P., Ploegh H. L., Strominger J. L. Comparison of amino acid sequences of two human histocompatibility antigens, HLA-A2 and HLA-B7: location of putative alloantigenic sites. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4395–4399. doi: 10.1073/pnas.76.9.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Orr H. T., López de Castro J. A., Lancet D., Strominger J. L. Complete amino acid sequence of a papain-solubilized human histocompatibility antigen, HLA-B7. 2. Sequence determination and search for homologies. Biochemistry. 1979 Dec 11;18(25):5711–5720. doi: 10.1021/bi00592a030. [DOI] [PubMed] [Google Scholar]
  27. Parham P., Alpert B. N., Orr H. T., Strominger J. L. Carbohydrate moiety of HLA antigens. Antigenic properties and amino acid sequences around the site of glycosylation. J Biol Chem. 1977 Nov 10;252(21):7555–7567. [PubMed] [Google Scholar]
  28. Parham P., McLean J. Characterization, evolution, and molecular basis of a polymorphic antigenic determinant shared by HLA-A and B products. Hum Immunol. 1980 Sep;1(2):131–139. doi: 10.1016/0198-8859(80)90100-7. [DOI] [PubMed] [Google Scholar]
  29. Patthy L., Smith E. L. Reversible modification of arginine residues. Application to sequence studies by restriction of tryptic hydrolysis to lysine residues. J Biol Chem. 1975 Jan 25;250(2):557–564. [PubMed] [Google Scholar]
  30. Poulik M. D., Reisfeld R. A. beta2-Microglobulins. Contemp Top Mol Immunol. 1975;4:157–204. [PubMed] [Google Scholar]
  31. Sanderson A. R. HL-A substances from human spleens. Nature. 1968 Oct 12;220(5163):192–195. doi: 10.1038/220192a0. [DOI] [PubMed] [Google Scholar]
  32. Schreier P. H., Bothwell A. L., Mueller-Hill B., Baltimore D. Multiple differences between the nucleic acid sequences of the IgG2aa and IgG2ab alleles of the mouse. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4495–4499. doi: 10.1073/pnas.78.7.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Slightom J. L., Blechl A. E., Smithies O. Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell. 1980 Oct;21(3):627–638. doi: 10.1016/0092-8674(80)90426-2. [DOI] [PubMed] [Google Scholar]
  34. Steinmetz M., Moore K. W., Frelinger J. G., Sher B. T., Shen F. W., Boyse E. A., Hood L. A pseudogene homologous to mouse transplantation antigens: transplantation antigens are encoded by eight exons that correlate with protein domains. Cell. 1981 Sep;25(3):683–692. doi: 10.1016/0092-8674(81)90175-6. [DOI] [PubMed] [Google Scholar]
  35. Tarr G. E., Beecher J. F., Bell M., McKean D. J. Polyquarternary amines prevent peptide loss from sequenators. Anal Biochem. 1978 Feb;84(2):622–7?0=ENG. doi: 10.1016/0003-2697(78)90086-6. [DOI] [PubMed] [Google Scholar]
  36. Trägärdh L., Rask L., Wiman K., Fohlman J., Peterson P. A. Complete amino acid sequence of pooled papain-solubilized HLA-A, -B, and -C antigens: relatedness to immunoglobulins and internal homologies. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1129–1133. doi: 10.1073/pnas.77.2.1129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Trägårdh L., Rask L., Wiman K., Peterson P. A. Primary structure of pooled, papain-solubilized HLA-A, -B, and -C antigens. Scand J Immunol. 1979;10(6):597–600. doi: 10.1111/j.1365-3083.1979.tb01395.x. [DOI] [PubMed] [Google Scholar]
  38. Tursz T., Fridman W. H., Senik A., Tsapis A., Fellous M. Human virus-infected target cells lacking HLA antigens resist specific T-lymphocyte cytolysis. Nature. 1977 Oct 27;269(5631):806–808. doi: 10.1038/269806a0. [DOI] [PubMed] [Google Scholar]

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