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. 1982 Aug 1;156(2):550–566. doi: 10.1084/jem.156.2.550

Biochemical characterization of a second family of human Ia molecules, HLA-DS, equivalent to murine I-A subregion molecules

PMCID: PMC2186769  PMID: 6808075

Abstract

In mice, two families of structurally distinct Ia molecules, one designated I-A and the other I-E, have been identified and characterized. The HLA-DR molecules represent one family of human Ia molecules equivalent to the murine I-E molecules on the basis of amino acid sequence homology. We describe the isolation and biochemical characterization of a second family of human Ia molecules, designated HLA-DS for second D-region locus, equivalent to the murine I-A molecules. The human HLA-DS molecules consist of two polypeptide chains, DS alpha (37,000 mol wt) and DS beta (29,000 mol wt), with 73% amino acid sequence identity to the murine I-A molecules. Furthermore, the HLA-DS molecules are closely linked genetically to HLA-DR molecules, a situation analogous to that observed in mice. The similarity in molecular weights of the DR and DS molecules might explain why others have failed to identify the latter in man.

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Selected References

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  1. Accolla R. S., Gross N., Carrel S., Corte G. Distinct forms of both alpha and beta subunits are present in the human Ia molecular pool. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4549–4551. doi: 10.1073/pnas.78.7.4549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allison J. P., Walker L. E., Russell W. A., Pellegrino M. A., Ferrone S., Reisfeld R. A., Frelinger J. A., Silver J. Murine Ia and human DR antigens: homology of amino-terminal sequences. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3953–3956. doi: 10.1073/pnas.75.8.3953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Asano Y., Singer A., Hodes R. J. Role of the major histocompatibility complex in T cell activation of B cell subpopulations. Major histocompatibility complex-restricted and -unrestricted B cell responses are mediated by distinct B cell subpopulations. J Exp Med. 1981 Oct 1;154(4):1100–1115. doi: 10.1084/jem.154.4.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhattacharya A., Dorf M. E., Springer T. A. A shared alloantigenic determinant on Ia antigens encoded by the I-A and I-E subregions: evidence for I region gene duplication. J Immunol. 1981 Dec;127(6):2488–2495. [PubMed] [Google Scholar]
  5. Clark R. B., Chiba J., Zweig S. E., Shevach E. M. T-cell colonies recognize antigen in association with specific epitopes on Ia molecules. Nature. 1982 Feb 4;295(5848):412–414. doi: 10.1038/295412a0. [DOI] [PubMed] [Google Scholar]
  6. Cook R. G., Siegelman M. H., Capra J. D., Uhr J. W., Vitetta E. S. Structural studies on the murine Ia alloantigens. IV. NH2-terminal sequence analysis of allelic products of the I-A and I-E/C subregions. J Immunol. 1979 Jun;122(6):2232–2237. [PubMed] [Google Scholar]
  7. Corte G., Calabi F., Damiani G., Bargellesi A., Tosi R., Sorrentino R. Human Ia molecules carrying DC1 determinants differ in both alpha- and beta-subunits from Ia molecules carrying DR determinants. Nature. 1981 Jul 23;292(5821):357–360. doi: 10.1038/292357a0. [DOI] [PubMed] [Google Scholar]
  8. Duquesnoy R. J., Marrari M., Annen K. Identification of an HLA-DR-associated system of B-cell alloantigens. Transplant Proc. 1979 Dec;11(4):1757–1760. [PubMed] [Google Scholar]
  9. Erb P., Feldmann M. The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens. J Exp Med. 1975 Aug 1;142(2):460–472. doi: 10.1084/jem.142.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fathman C. G., Kimoto M., Melvold R., David C. S. Reconstitution of Ir genes, Ia antigens, and mixed lymphocyte reaction determinants by gene complementation. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1853–1857. doi: 10.1073/pnas.78.3.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Freed J. H., David C. S., Shreffler D. C., Nathenson S. G. Structural studies of the protein portion of the H-2-linked Ia glycoprotein antigens of the mouse: tryptic peptide comparison of products from the I-A and I-C subregions of B10-HTT. J Immunol. 1978 Jul;121(1):91–97. [PubMed] [Google Scholar]
  12. Goyert S. M., Silver J. Isolation of I-A subregion-like molecules from subhuman primates and man. Nature. 1981 Nov 19;294(5838):266–268. doi: 10.1038/294266a0. [DOI] [PubMed] [Google Scholar]
  13. Jones P. P., Murphy D. B., McDevitt H. O. Two-gene control of the expression of a murine Ia antigen. J Exp Med. 1978 Oct 1;148(4):925–939. doi: 10.1084/jem.148.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kappler J. W., Marrack P. C. Helper T cells recognise antigen and macrophage surface components simultaneously. Nature. 1976 Aug 26;262(5571):797–799. doi: 10.1038/262797a0. [DOI] [PubMed] [Google Scholar]
  15. Kappler J. W., Marrack P. The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression. J Exp Med. 1978 Dec 1;148(6):1510–1522. doi: 10.1084/jem.148.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kappler J. W., Marrack P. The role of H-2-linked genes in helper T-cell function. I. In vitro expression in B cells of immune response genes controlling helper T-cell activity. J Exp Med. 1977 Dec 1;146(6):1748–1764. doi: 10.1084/jem.146.6.1748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Karr R. W., Kannapell C. C., Stein J. A., Gebel H. M., Mann D. L., Duquesnoy R. J., Fuller T. C., Rodey G. E., Schwartz B. D. Molecular relationships of the human B cell alloantigens, MT2, MB3, MT4, and DR5. J Immunol. 1982 Apr;128(4):1809–1818. [PubMed] [Google Scholar]
  18. Katz D. H., Graves M., Dorf M. E., Dimuzio H., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex. J Exp Med. 1975 Jan 1;141(1):263–268. doi: 10.1084/jem.141.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  20. Lampson L. A., Levy R. Two populations of Ia-like molecules on a human B cell line. J Immunol. 1980 Jul;125(1):293–299. [PubMed] [Google Scholar]
  21. Markert M. L., Cresswell P. Polymorphism of human B-cell alloantigens: evidence for three loci within the HLA system. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6101–6104. doi: 10.1073/pnas.77.10.6101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McMillan M., Frelinger J. A., Jones P. P., Murphy D. B., McDevitt H. O., Hood L. Structure of murine Ia antigens. Two dimensional electrophoretic analyses and high pressure liquid chromatography tryptic peptide maps of products of the I-A and I-E subregions and of an associated invariant polypeptide. J Exp Med. 1981 Apr 1;153(4):936–950. doi: 10.1084/jem.153.4.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Michaelides M., Sandrin M., Morgan G., McKenzie I. F., Ashman R., Melvold R. W. Ir gene function in an I-A subregion mutant B6.C-H-2bm12. J Exp Med. 1981 Feb 1;153(2):464–469. doi: 10.1084/jem.153.2.464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. Role of major histocompatibility complex gene products in delayed-type hypersensitivity. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2486–2490. doi: 10.1073/pnas.73.7.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. O'Farrell P. Z., Goodman H. M., O'Farrell P. H. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. doi: 10.1016/0092-8674(77)90176-3. [DOI] [PubMed] [Google Scholar]
  26. Paul W. E., Shevach E. M., Pickeral S., Thomas D. W., Rosenthal A. S. Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells. J Exp Med. 1977 Mar 1;145(3):618–630. doi: 10.1084/jem.145.3.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pierres M., Devaux C., Dosseto M., Marchetto S. Clonal analysis of B- and T-cell responses to Ia antigens. I. Topology of epitope regions on I-Ak and I-Ek molecules analyzed with 35 monoclonal alloantibodies. Immunogenetics. 1981 Dec;14(6):481–495. doi: 10.1007/BF00350120. [DOI] [PubMed] [Google Scholar]
  28. Schwartz R. H., David C. S., Dorf M. E., Benacerraf B., Paul W. E. Inhibition of dual Ir gene-controlled T-lymphocyte proliferative response to poly (Glu56Lys35Phe9)n with anti-Ia antisera directed against products of either I-A or I-C subregion. Proc Natl Acad Sci U S A. 1978 May;75(5):2387–2391. doi: 10.1073/pnas.75.5.2387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shackelford D. A., Mann D. L., van Rood J. J., Ferrara G. B., Strominger J. L. Human B-cell alloantigens DC1, MT1, and LB12 are identical to each other but distinct from the HLA-DR antigen. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4566–4570. doi: 10.1073/pnas.78.7.4566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Silver J., Cecka J. M., McMillan M., Hood L. Chemical characterization of products of the H-2 complex. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):369–377. doi: 10.1101/sqb.1977.041.01.044. [DOI] [PubMed] [Google Scholar]
  31. Silver J. Microsequence analysis in automated spinning-cup sequenators. Methods Enzymol. 1977;47:247–260. doi: 10.1016/0076-6879(77)47029-0. [DOI] [PubMed] [Google Scholar]
  32. Silver J., Russell W. A. Structural polymorphism of I-E subregion antigens determined by a gene in the H-2K to I-B genetic interval. Nature. 1979 May 31;279(5712):437–439. doi: 10.1038/279437a0. [DOI] [PubMed] [Google Scholar]
  33. Silver J., Walker L. E., Reisfeld R. A., Pellegrino M. A., Ferrone S. Structural studies of murine I-E and human DR antigens. Mol Immunol. 1979 Jan;16(1):37–42. doi: 10.1016/0161-5890(79)90025-7. [DOI] [PubMed] [Google Scholar]
  34. Singer A., Hathcock K. S., Hodes R. J. Self recognition in allogeneic radiation bone marrow chimeras. A radiation-resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells. J Exp Med. 1981 May 1;153(5):1286–1301. doi: 10.1084/jem.153.5.1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Singer A., Hathcock K. S., Hodes R. J. Self recognition in allogeneic thymic chimeras. Self recognition by T helper cells from thymus-engrafted nude mice is restricted to the thymic H-2 haplotype. J Exp Med. 1982 Jan 1;155(1):339–344. doi: 10.1084/jem.155.1.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sprent J. Effects of blocking helper T cell induction in vivo with anti-Ia antibodies. Possible role of I-A/E hybrid molecules as restriction elements. J Exp Med. 1980 Oct 1;152(4):996–1010. doi: 10.1084/jem.152.4.996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sprent J. Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. II. Evidence for restrictions affecting helper cell induction and T-B collaboration, both mapping to the K-end of the H-2 complex. J Exp Med. 1978 Apr 1;147(4):1159–1174. doi: 10.1084/jem.147.4.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sprent J. Restricted helper function of F1 leads to parent bone marrow chimeras controlled by K-end of H-2 complex. J Exp Med. 1978 Jun 1;147(6):1838–1842. doi: 10.1084/jem.147.6.1838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Springer T. A., Kaufman J. F., Terhorst C., Strominger J. L. Purification and structural characterisation of human HLA-linked B-cell antigens. Nature. 1977 Jul 21;268(5617):213–218. doi: 10.1038/268213a0. [DOI] [PubMed] [Google Scholar]
  40. Sredni B., Volkman D., Schwartz R. H., Fauci A. S. Antigen-specific human T-cell clones: development of clones requiring HLA-DR-compatible presenting cells for stimulation in presence of antigen. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1858–1862. doi: 10.1073/pnas.78.3.1858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Suciu-Foca N., Godfrey M., Rohowsky C., McKiernan P., Susinno E., Broell J. Evidence that HLA-D is different from DR and that two different HLA loci code for B-cell antigens. Transplant Proc. 1979 Dec;11(4):1781–1787. [PubMed] [Google Scholar]
  42. Suciu-Foca N., Rohowsky C., McKiernan P., Godfrey M., Susinno E., Broell J., Hardy M. Association of Dw9 with DRw2. Transplant Proc. 1979 Dec;11(4):1799–1803. [PubMed] [Google Scholar]
  43. Swierkosz J. E., Marrack P., Kappler J. W. The role of H-2-linked genes in helper T cell function. V. I-region control of helper T cell interaction with antigen-presenting macrophages. J Immunol. 1979 Aug;123(2):654–659. [PubMed] [Google Scholar]
  44. Swierkosz J. E., Rock K., Marrack P., Kappler J. W. The role of H-2 linked genes in helper T-cell function. II. Isolation on antigen-pulsed macrophages of two separate populations of F1 helper T cells each specific for antigen and one set of parental H-2 products. J Exp Med. 1978 Feb 1;147(2):554–570. doi: 10.1084/jem.147.2.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Symington F. W., Sprent J. A monoclonal antibody detecting an Ia specificity mapping in the I-A or I-E subregion. Immunogenetics. 1981;14(1-2):53–61. doi: 10.1007/BF00344299. [DOI] [PubMed] [Google Scholar]
  46. Tosi R., Tanigaki N., Centis D., Ferrara G. B., Pressman D. Immunological dissection of human Ia molecules. J Exp Med. 1978 Dec 1;148(6):1592–1611. doi: 10.1084/jem.148.6.1592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Uhr J. W., Capra J. D., Vitetta E. S., Cook R. G. Organization of the immune response genes. Science. 1979 Oct 19;206(4416):292–297. doi: 10.1126/science.113876. [DOI] [PubMed] [Google Scholar]
  48. Waldmann H., Pope H., Beetles C., Davies A. J. The influence of thymus on the development of MHC restrictions exhibited by T-helper cells. Nature. 1979 Jan 11;277(5692):137–138. doi: 10.1038/277137a0. [DOI] [PubMed] [Google Scholar]
  49. Weyand C., Hämmerling G. J., Goronzy J. Recognition of H-2 domains by cytotoxic T lymphocytes. Nature. 1981 Aug 13;292(5824):627–629. doi: 10.1038/292627a0. [DOI] [PubMed] [Google Scholar]
  50. von Boehmer H., Haas W., Jerne N. K. Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice. Proc Natl Acad Sci U S A. 1978 May;75(5):2439–2442. doi: 10.1073/pnas.75.5.2439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. von Boehmer H., Hudson L., Sprent J. Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras. J Exp Med. 1975 Oct 1;142(4):989–997. doi: 10.1084/jem.142.4.989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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