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. 1982 Mar 1;155(3):749–767. doi: 10.1084/jem.155.3.749

The QA2 subregion controls the expression of two antigens recognized by H-2- unrestricted cytotoxic T cells

J Forman, J Trial, S Tonkonogy, L Flaherty
PMCID: PMC2186634  PMID: 6174664

Abstract

B6.KI mice were immunized with spleen cells from B6.K2, a Qa2-subregion congenic strain. Cytotoxic T cells were generated that recognize two target antigens controlled by this region. One of the target antigens is Qa-2. This was demonstrated by the findings that pretreatment of target cells with monoclonal anti-Qa-2 antibody blocked lysis of target cells, and Qa-2 target antigens and serological determinants had a concordant distribution on a panel of B10.W (wild) mice. The gene controlling the Qa-2 target antigen is not polymorphic because B6.K2 and three strains of Qa-2(+) B10.W mice express the same antigens, as determined by a CTL cold target competition assay. Anti-Qa-2 CTL were H-2 unrestricted because effector cells lysed Qa-2(+) targets irrespective of their H-2 haplotype, including five B 10.W strains, and lysis was not inhibited by pretreating target cells with anti-H-2 sera. The Qa2 subregion does not act as a restricting locus for anti-minor-H antigen CTL. A second target antigen was detected that was associated with the expression of the Qa-5 determinant. However, CTL activity could not be blocked by pretreating target cells with monoclonal anti-Qa-5. Therefore, the CTL target antigen may be expressed on a Qa-5(-) molecule. Although the Qa-5 associated CTL specificity is only detected on H-2D(b) strains, it is unlikely that CTL recognition is H-2 restricted because anti-H-2(b) sera has no effect in blocking this reactivity. Qa-2 and H-2 class I antigens share a similar structure and serve as target antigens for unrestricted CTL. However, unlike class I H-2 genes, Qa-2 neither restricts antigen-specific CTL nor is polymorphie. Therefore, it is likely that Qa-2 and H-2 are derived from a common ancestral gene and have evolved to serve different functions.

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Selected References

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  1. Bevan M. J. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J Exp Med. 1975 Dec 1;142(6):1349–1364. doi: 10.1084/jem.142.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown J. L., Kato K., Silver J., Nathenson S. G. Notable diversity in peptide composition of murine H-2K and H-2D alloantigens. Biochemistry. 1974 Jul 16;13(15):3174–3178. doi: 10.1021/bi00712a027. [DOI] [PubMed] [Google Scholar]
  3. Cantor H., Hugenberger J., McVay-Boudreau L., Eardley D. D., Kemp J., Shen F. W., Gershon R. K. Immunoregulatory circuits among T-cell sets. Identification of a subpopulation of T-helper cells that induces feedback inhibition. J Exp Med. 1978 Oct 1;148(4):871–877. doi: 10.1084/jem.148.4.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohn M., Epstein R. T-cell inhibition of humoral responsiveness. II. Theory on the role of restrictive recognition in immune regulation. Cell Immunol. 1978 Aug;39(1):125–153. doi: 10.1016/0008-8749(78)90089-8. [DOI] [PubMed] [Google Scholar]
  5. Coligan J. E., Kindt T. J., Ewenstein B. M., Uehara H., Nisizawa T., Nathenson S. G. Primary structure of murine major histocompatibility complex alloantigens: amino acid sequence studies of the cyanogen bromide fragments of the H-2Kb glycoprotein. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3390–3394. doi: 10.1073/pnas.75.7.3390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eardley D. D., Hugenberger J., McVay-Boudreau L., Shen F. W., Gershon R. K., Cantor H. Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition. J Exp Med. 1978 Apr 1;147(4):1106–1115. doi: 10.1084/jem.147.4.1106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Flaherty L., Zimmerman D., Sullivan K. A. Qa-2 and Qa-3 antigens on lymphocyte subpopulations. I. Mitogen responsiveness. J Immunol. 1978 Nov;121(5):1640–1643. [PubMed] [Google Scholar]
  8. Forman J. H-2 unrestricted cytotoxic T cell activity against antigens controlled by genes in the QA/TLA region. J Immunol. 1979 Dec;123(6):2451–2455. [PubMed] [Google Scholar]
  9. Forman J. On the role of the H-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets. J Exp Med. 1975 Aug 1;142(2):403–418. doi: 10.1084/jem.142.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Gomard E., Duprez V., Reme T., Colombani M. J., Levy J. P. Exclusive involvement of H-2Db or H-2Kd product in the interaction between T-killer lymphocytes and syngeneic H-2b or H-2d viral lymphomas. J Exp Med. 1977 Oct 1;146(4):909–922. doi: 10.1084/jem.146.4.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hämmerling G. J., Hämmerling U., Flaherty L. Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies. J Exp Med. 1979 Jul 1;150(1):108–116. doi: 10.1084/jem.150.1.108. [DOI] [PMC free article] [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. Kastner D. L., Rich R. R. H-2-nonrestricted cytotoxic responses to an antigen encoded telomeric to H-2D. J Immunol. 1979 Jan;122(1):196–201. [PubMed] [Google Scholar]
  15. Kincade P. W., Flaherty L., Lee G., Watanabe T., Michaelson J. Qa antigen expression on functional lymphoid, myeloid, and stem cells in adult mice. J Immunol. 1980 Jun;124(6):2879–2885. [PubMed] [Google Scholar]
  16. Klein J. The major histocompatibility complex of the mouse. Science. 1979 Feb 9;203(4380):516–521. doi: 10.1126/science.104386. [DOI] [PubMed] [Google Scholar]
  17. Koo G. C., Jacobson J. B., Hammerling G. J., Hammerling U. Antigenic profile of murine natural killer cells. J Immunol. 1980 Sep;125(3):1003–1006. [PubMed] [Google Scholar]
  18. Michaelson J., Flaherty L., Bushkin Y., Yudkowitz H. Further biochemical data on Qa-2. Immunogenetics. 1981;14(1-2):129–140. doi: 10.1007/BF00344306. [DOI] [PubMed] [Google Scholar]
  19. Michaelson J., Flaherty L., Vitetta E., Poulik M. D. Molecular similarities between the Qa-2 alloantigen and other gene products of the 17th chromosome of the mouse. J Exp Med. 1977 Apr 1;145(4):1066–1070. doi: 10.1084/jem.145.4.1066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nell L. J., Kastner D. L., Rich R. R. Qa-1-associated antigens. III. Distribution of Qa-1 region antigens on lymphoid subpopulations. J Immunol. 1980 Dec;125(6):2597–2603. [PubMed] [Google Scholar]
  21. Soloski M. J., Uhr J. W., Flaherty L., Vitetta E. S. Qa-2, H-2K, and H-2D alloantigens evolved from a common ancestral gene. J Exp Med. 1981 May 1;153(5):1080–1093. doi: 10.1084/jem.153.5.1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sullivan K. A., Flaherty L. The Qa-2 antigen on lymphocyte subpopulations. Mixed lymphocyte culture and cell-mediated lympholysis. J Immunol. 1979 Dec;123(6):2920–2924. [PubMed] [Google Scholar]
  23. Zaleska-Rutczynska Z., Klein J. Histocompatibility-2 system in wild mice. V. Serologic analysis of sixteen B10.W congenic lines. J Immunol. 1977 Dec;119(6):1903–1911. [PubMed] [Google Scholar]
  24. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

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