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. 1980 May 1;151(5):993–1013. doi: 10.1084/jem.151.5.993

Fine specificity of alloimmune cytotoxic T lymphocytes directed against H-2K. A study with Kb mutants

PMCID: PMC2185858  PMID: 6154770

Abstract

The fine specificity of alloimmune cytotoxic T lymphocytes (CTL) was investigated in CTL responses across the smallest known H-2 differences, those based on mutation at a single H-2 locus. CTL were generated in all possible mixed lymphocyte culture (MLC) combinations among seven H-2Kb mutants and the mouse strain of origin, C57BL/6 (B6-H- 2b). CTL were also generated in all F1 hybrid responder/homozygous stimulator-cell combinations among four Kb mutants and B6-H-2b. CTL activity was measured in cell-mediated lympholysis (CML) against target cells from all Kb mutants and B6-H-2b. Cross-reactivity against targets other than the MLC stimulator was extensive and led to the distinction of 64 CML target determinants. Two Kb mutants (B6-H-2bm6 and B6.C-H- 2bm9) showed identical typing for all 64 CML determinants. CML reactions after MLC between these two haplotypes were mutually negative. The mutants B6-H-2bm3 and B6.C-H-2bm11 showed identical typing for 47 of the 64 determinants. Their close relationship is in agreement with the finding that H-2bm3 anti-H-2bm11 CTL were the only ones that exclusively lysed target cells of stimulator-cell genotype. On the basis of CML typing, the sequence of relatedness of the mutants with H-2b is as follows: bm6/bm9-bm10-bm3-bm1-bm11, bm6/bm9 being the closest to, and bm11 the most distant from H-2b. The extensive cross- reactivity of alloimmune CTL appears to reflect immunogenetic complexity rather than lack of specificity. Comparison with other reports supports the notion that the system of Kb CML determinants, recognized by alloimmune CTL, is at least partially overlapping with the H-2Kb specificity repertoire involved in the associative T cell recognition of virus-infected cells.

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Selected References

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  1. Bailey D. W., Kohn H. I. Inherited histocompatibility changes in progeny of irradiated and unirradiated inbred mice. Genet Res. 1965 Nov;6(3):330–340. doi: 10.1017/s0016672300004225. [DOI] [PubMed] [Google Scholar]
  2. Berke G., Amos D. B. Cytotoxic lymphocytes in the absence of detectable antibody. Nat New Biol. 1973 Apr 25;242(121):237–239. doi: 10.1038/newbio242237a0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Brown J. L., Nathenson S. G. Structural differences between parent and mutant H-2K glycoproteins from two H-2K gene mutants: b6.c-h-2ba (Hzl) and B6-H-2bd (M505). J Immunol. 1977 Jan;118(1):98–102. [PubMed] [Google Scholar]
  5. Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
  6. Finberg R., Burakoff S. J., Cantor H., Benacerraf B. Biological significance of alloreactivity: T cells stimulated by Sendai virus-coated syngeneic cells specifically lyse allogeneic target cells. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5145–5149. doi: 10.1073/pnas.75.10.5145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Geib R., Chiang C., Klein J. Evidence for multiple clones of cytotoxic T cells responding to antigenic determinants on the same molecule. J Immunol. 1978 Jan;120(1):340–342. [PubMed] [Google Scholar]
  8. Gillis S., Baker P. E., Ruscetti F. W., Smith K. A. Long-term culture of human antigen-specific cytotoxic T-cell lines. J Exp Med. 1978 Oct 1;148(4):1093–1098. doi: 10.1084/jem.148.4.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Klein J., Egorov I. K. Graft-vs-host reaction with an H-2 mutant. J Immunol. 1973 Sep;111(3):976–979. [PubMed] [Google Scholar]
  10. Klein J. H-2 mutations: their genetics and effect on immune functions. Adv Immunol. 1978;26:55–146. doi: 10.1016/s0065-2776(08)60229-1. [DOI] [PubMed] [Google Scholar]
  11. Klein J., Hauptfeld M., Hauptfeld V. Serological distinction of mutants B6.CH(zl) and B6.M505 from strain C57BL-6. J Exp Med. 1974 Oct 1;140(4):1127–1132. doi: 10.1084/jem.140.4.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kohn H. I., Melvold R. W. Spontaneous histocompatibility mutations detected by dermal grafts: significant changes in rate over a 10-year period in the mouse H-system. Mutat Res. 1974 Aug;24(2):163–169. doi: 10.1016/0027-5107(74)90129-8. [DOI] [PubMed] [Google Scholar]
  13. Melief C. J., van der Meulen M. Y., Christiaans B. J., de Greeve P. Cooperation between subclass of T lymphocytes in the in vitro generation of cytotoxicity against a mutant H-2K difference. An analysis with anti-Lyt antisera. Eur J Immunol. 1979 Jan;9(1):7–12. doi: 10.1002/eji.1830090103. [DOI] [PubMed] [Google Scholar]
  14. Nabholz M., Engers H. D., Collavo D., North M. Cloned T-cell lines with specific cytolytic activity. Curr Top Microbiol Immunol. 1978;81:176–187. doi: 10.1007/978-3-642-67448-8_29. [DOI] [PubMed] [Google Scholar]
  15. Shearer G. M., Rehn T. G., Schmitt-Verhulst A. M. Role of the murine major histocompatibility complex in the specificity of in vitro T-cell-mediated lympholysis against chemically-modified autologous lymphocytes. Transplant Rev. 1976;29:222–246. doi: 10.1111/j.1600-065x.1976.tb00203.x. [DOI] [PubMed] [Google Scholar]
  16. Shreffler D. C., David C. S. The H-2 major histocompatibility complex and the I immune response region: genetic variation, function, and organization. Adv Immunol. 1975;20:125–195. doi: 10.1016/s0065-2776(08)60208-4. [DOI] [PubMed] [Google Scholar]
  17. Simpson E., Gordon R. D. Responsiveness to HY antigen Ir gene complementation and target cell specificity. Immunol Rev. 1977;35:59–75. doi: 10.1111/j.1600-065x.1977.tb00235.x. [DOI] [PubMed] [Google Scholar]
  18. Simpson E., Mobraaten L., Chandler P., Hetherington C., Hurme M., Brunner C., Bailey D. Cross-reactive cytotoxic responses. H-2 restricted are more specific than anti-H-2 responses. J Exp Med. 1978 Dec 1;148(6):1478–1487. doi: 10.1084/jem.148.6.1478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Snell G. D. T cells, T cells recognition structures, and the major histocompatibility complex. Immunol Rev. 1978;38:3–69. doi: 10.1111/j.1600-065x.1978.tb00384.x. [DOI] [PubMed] [Google Scholar]
  20. Widmer M. B., Alter B. J., Bach F. H., Bach M. L. Lymphocyte reactivity to serologically undetected components of the major histocompatibility complex. Nat New Biol. 1973 Apr 25;242(121):239–241. doi: 10.1038/newbio242239a0. [DOI] [PubMed] [Google Scholar]
  21. Wohlgemuth A. Abstract immunogenetic systems. J Theor Biol. 1978 Aug 8;73(3):469–508. doi: 10.1016/0022-5193(78)90154-6. [DOI] [PubMed] [Google Scholar]
  22. Zinkernagel R. M., Doherty P. C. H-2 compatability requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificities are associated with structures coded for in H-2K or H-2D;. J Exp Med. 1975 Jun 1;141(6):1427–1436. doi: 10.1084/jem.141.6.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zinkernagel R. M. H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. The H-2K structure involved is coded by a single cistron defined by H-2Kb mutant mice. J Exp Med. 1976 Feb 1;143(2):437–443. doi: 10.1084/jem.143.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zinkernagel R. M. Thymus and lymphohemopoietic cells: their role in T cell maturation in selection of T cells' H-2-restriction-specificity and in H-2 linked Ir gene control. Immunol Rev. 1978;42:224–270. doi: 10.1111/j.1600-065x.1978.tb00264.x. [DOI] [PubMed] [Google Scholar]
  25. von Boehmer H., Hengartner H., Nabholz M., Lernhardt W., Schreier M. H., Haas W. Fine specificity of a continuously growing killer cell clone specific for H-Y antigen. Eur J Immunol. 1979 Aug;9(8):592–597. doi: 10.1002/eji.1830090804. [DOI] [PubMed] [Google Scholar]

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