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. 1982 Jan 1;155(1):303–320. doi: 10.1084/jem.155.1.303

Immune response genes controlling responsiveness to major transplantation antigens. Specific major histocompatibility complex- linked defect for antibody responses to class I alloantigens

PMCID: PMC2186570  PMID: 6172542

Abstract

We have identified two major histocompatibility complex (MHC)-linked Ir genes that control the antibody response made by rats against class I major alloantigens. We have named these genes Ir-RT1Aa and Ir-RT1Ac. These Ir genes determine responsiveness of the immunized animal in a typical codominant fashion. There is no evidence so far for trans- complementation between low-responder haplotypes. Detailed studies of Ir-RT1Aa indicate that it controls the antibody response to at least two distinct alloantigenic determinants on RT1Aa molecules. These class I molecules thus behave like hapten-carrier conjugates when the response against the carrier is under Ir gene control. Analysis of the origin of alloantibody-forming cells in tetraparental radiation chimeras indicates that Ir-RT1Aa must control the provision of effective help to B cells. In many respects therefore, the properties of Ir-RT1Aa are broadly similar to those described for Ir genes controlling antibody responses to conventional antigens. The existence of apparently conventional Ir genes controlling the antibody response to major alloantigens strongly suggest that the processing of these transmembrane molecules by host antigen-presenting cells is a prerequisite for immune induction, and that it is the MHC of the responder rather than that of the allograft to which T helper cells are restricted in alloimmune responses in vivo.

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Selected References

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  1. Araneo B. A., Yowell R. L., Metzger D. W., Sercarz E. E. Positive selection of major histocompatibility complex-restricted suppressor T cells bearing the predominant idiotype in the immune response to lysozyme. Proc Natl Acad Sci U S A. 1981 Jan;78(1):499–503. doi: 10.1073/pnas.78.1.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Butcher G. W., Howard J. C. A recombinant in the major histocompatibility complex of the rat. Nature. 1977 Mar 24;266(5600):362–364. doi: 10.1038/266362a0. [DOI] [PubMed] [Google Scholar]
  3. Butcher G. W., Licence D. R., Roser B. J. The genetics of the graft-versus-host reactions in rats: strength of reaction against RT1.A and RT1.B antigens alone and in combination. Transplant Proc. 1981 Jun;13(2):1375–1377. [PubMed] [Google Scholar]
  4. Chisholm P. M., Smith M. E., Sparshott S. M., Ford W. L. A comparison of immune responses against AG-B and non-AG-B antigens, presented alone or together. Transplantation. 1977 Jun;23(6):470–478. doi: 10.1097/00007890-197706000-00003. [DOI] [PubMed] [Google Scholar]
  5. Davidson W. F., Parish C. R. A procedure for removing red cells and dead cells from lymphoid cell suspensions. J Immunol Methods. 1975 Jun;7(2-3):291–300. doi: 10.1016/0022-1759(75)90026-5. [DOI] [PubMed] [Google Scholar]
  6. Dorf M. E., Stimpfling J. H. Coupled complementation of immune response genes controlling responsiveness to the H-2.2 alloantigen. J Exp Med. 1977 Aug 1;146(2):571–578. doi: 10.1084/jem.146.2.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Erb P., Meier B., Kraus D., von Boehmer H., Feldmann M. Nature of T cell-macrophage interaction in helper cell induction in vitro. I. Evidence for genetic restriction of T cell-macrophage interactions prior to T cell priming. Eur J Immunol. 1978 Nov;8(11):786–792. doi: 10.1002/eji.1830081107. [DOI] [PubMed] [Google Scholar]
  8. Galfre G., Howe S. C., Milstein C., Butcher G. W., Howard J. C. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature. 1977 Apr 7;266(5602):550–552. doi: 10.1038/266550a0. [DOI] [PubMed] [Google Scholar]
  9. Gallico G. G., Butcher G. W., Howard J. C. The role of subregions of the rat major histocompatibility complex in the rejection and passive enhancement of renal allografts. J Exp Med. 1979 Jan 1;149(1):244–253. doi: 10.1084/jem.149.1.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Günther E., Stark O., Koch C. Genetic definition of I region-determined antigens of the rat major histocompatibility complex. Eur J Immunol. 1978 Mar;8(3):206–212. doi: 10.1002/eji.1830080313. [DOI] [PubMed] [Google Scholar]
  11. Haustein D., Günther E. Biochemical analysis of gene products of major histocompatibility recombinant haplotypes in the rat. Eur J Immunol. 1980 Aug;10(8):615–620. doi: 10.1002/eji.1830100808. [DOI] [PubMed] [Google Scholar]
  12. Howard J. C., Butcher G. W., Galfrè G., Milstein C., Milstein C. P. Monoclonal antibodies as tools to analyze the serological and genetic complexities of major transplantation antigens. Immunol Rev. 1979;47:139–174. doi: 10.1111/j.1600-065x.1979.tb00292.x. [DOI] [PubMed] [Google Scholar]
  13. Howard J. C., Corvalan J. R. Demonstration of MHC-specific haemolytic plaque-forming cells. Nature. 1979 Mar 29;278(5703):449–451. doi: 10.1038/278449a0. [DOI] [PubMed] [Google Scholar]
  14. Howard J. C., Gowans J. L. The role of lymphocytes in antibody formation. 3. The origin from small lymphocytes of cells forming direct and indirect haemolytic plaques to sheep erythrocytes in the rat. Proc R Soc Lond B Biol Sci. 1972 Sep 19;182(1067):193–209. doi: 10.1098/rspb.1972.0075. [DOI] [PubMed] [Google Scholar]
  15. Korngold R., Sprent J. Selection of cytotoxic T-cell precursors specific for minor histocompatibility determinants. I. Negative selection across H-2 barriers induced with disrupted cells but not with glutaraldehyde-treated cells: evidence for antigen processing. J Exp Med. 1980 Feb 1;151(2):314–327. doi: 10.1084/jem.151.2.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Köhler G., Milstein C. Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur J Immunol. 1976 Jul;6(7):511–519. doi: 10.1002/eji.1830060713. [DOI] [PubMed] [Google Scholar]
  17. Lake P., Douglas T. C. Recognition and genetic control of helper determinants for cell surface antigen Thy-1. Nature. 1978 Sep 21;275(5677):220–222. doi: 10.1038/275220a0. [DOI] [PubMed] [Google Scholar]
  18. Matzinger P., Bevan M. J. Induction of H-2-restricted cytotoxic T cells: in vivo induction has the appearance of being unrestricted. Cell Immunol. 1977 Sep;33(1):92–100. doi: 10.1016/0008-8749(77)90137-x. [DOI] [PubMed] [Google Scholar]
  19. Mozes E., McDevitt H. O. The effect of genetic control of immune response to synthetic polypeptides on the response to homologous DNP-polypeptide conjugates. Immunochemistry. 1969 Sep;6(5):760–762. doi: 10.1016/0019-2791(67)90141-3. [DOI] [PubMed] [Google Scholar]
  20. Press J. L., McDevitt H. O. Allotype-specific analysis of anti-(Tyr,Glu)-Ala-Lys antibodies produced by Ir-1A high and low responder chimeric mice. J Exp Med. 1977 Dec 1;146(6):1815–1820. doi: 10.1084/jem.146.6.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rolstad B., Williams A. F., Ford W. L. The alloantibody response to a strong transplantation antigen (Ag-B). Quantitative aspects and thymus dependence of the response. Transplantation. 1974 Apr;17(4):416–423. doi: 10.1097/00007890-197404000-00013. [DOI] [PubMed] [Google Scholar]
  22. Scott D. W., Howard J. C. Collaboration between thymus-derived and marrow-derived thoracic duct lymphocytes in the hemolysin response of the rat. Cell Immunol. 1972 Mar;3(3):430–441. doi: 10.1016/0008-8749(72)90248-1. [DOI] [PubMed] [Google Scholar]
  23. Shih W. W., Matzinger P. C., Swain S. L., Dutton R. W. Analysis of histocompatibility requirements for proliferative and helper T cell activity. T cell populations depleted of alloreactive cells by negative selection. J Exp Med. 1980 Nov 1;152(5):1311–1328. doi: 10.1084/jem.152.5.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Singer A., Hathcock K. S., Hodes R. J. Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells. J Exp Med. 1979 May 1;149(5):1208–1226. doi: 10.1084/jem.149.5.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sprent J. Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. I. Failure to collaborate with B cells of the opposite parental strain not associated with active suppression. J Exp Med. 1978 Apr 1;147(4):1142–1158. doi: 10.1084/jem.147.4.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Warner C. M., Berntson T. J., Eakley L., McIvor J. L., Newton R. C. The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody. J Exp Med. 1978 Jun 1;147(6):1849–1853. doi: 10.1084/jem.147.6.1849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weinberger O., Herrmann S., Mescher M. F., Benacerraf B., Burakoff S. J. Antigen-presenting cell function in induction of helper T cells for cytotoxic T-lymphocyte responses: evidence for antigen processing. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1796–1799. doi: 10.1073/pnas.78.3.1796. [DOI] [PMC free article] [PubMed] [Google Scholar]

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