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. 1980 Jan 1;151(1):235–245. doi: 10.1084/jem.151.1.235

Human cytotoxic T-cell responses to type A and type B influenza viruses can be restricted by different HLA antigens. Implications for HLA polymorphism and genetic regulation

PMCID: PMC2185747  PMID: 6153112

Abstract

The present study compares human cytotoxic T-cell responses to two closely related viruses (type A and type B influenza) to understand the antigen-specific elements involved in HLA-linked genetic control of cytotoxic T-cell responses. The HLA antigens function as self antigens that are recognized by cytotoxic T cells sensitized against either virus. However, studies in an informative family indicate that in this family, the HLA antigens preferentially recognized in conjunction with type A influenza (A/HK) differ from the HLA antigens preferentially recognized in conjunction with type B influenza (B/HK). Similarly, population studies demonstrate that some (but not all) donors whose T cells recognized A/HK in conjunction with HLA-A2 failed to recognize B/HK in conjunction with HLA-A2. Thus, HLA-linked regulation must operate by a mechanism(s) that is specific both for the self HLA antigen and the viral antigen. Furthermore, these findings indicate that different HLA antigens may facilitate T-cell responses to different pathogens, which would result in an evolutionary advantage for HLA heterozygosity.

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Selected References

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

  1. Bevan M. J. In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells. Nature. 1977 Sep 29;269(5627):417–418. doi: 10.1038/269417a0. [DOI] [PubMed] [Google Scholar]
  2. Biddison W. E., Shaw S. Differences in HLA antigen recognition by human influenza virus-immune cytotoxic T cells. J Immunol. 1979 May;122(5):1705–1709. [PubMed] [Google Scholar]
  3. Biddison W. E., Shaw S., Nelson D. L. Virus specificity of human influenza virus-immune cytotoxic T cells. J Immunol. 1979 Feb;122(2):660–664. [PubMed] [Google Scholar]
  4. 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]
  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. Doherty P. C., Zinkernagel R. M. A biological role for the major histocompatibility antigens. Lancet. 1975 Jun 28;1(7922):1406–1409. doi: 10.1016/s0140-6736(75)92610-0. [DOI] [PubMed] [Google Scholar]
  7. Fazekas de St Groth, Webster R. G. Disquisitions of Original Antigenic Sin. I. Evidence in man. J Exp Med. 1966 Sep 1;124(3):331–345. doi: 10.1084/jem.124.3.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goulmy E., Termijtelen A., Bradley B. A., van Rood J. J. Y-antigen killing by T cells of women is restricted by HLA. Nature. 1977 Apr 7;266(5602):544–545. doi: 10.1038/266544a0. [DOI] [PubMed] [Google Scholar]
  9. Hurme M., Hetherington C. M., Chandler P. R., Simpson E. Cytotoxic T-cell responses to H-Y: mapping of the Ir genes. J Exp Med. 1978 Mar 1;147(3):758–767. doi: 10.1084/jem.147.3.758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Levy R. B., Shearer G. M. Regulation of T-cell-mediated lympholysis by the murine major histocompatibility complex. I. Preferential in vitro responses to trinitrophenyl-modified self K- and D-coded gene products in parental and F1 hybrid mouse strains. J Exp Med. 1979 Jun 1;149(6):1379–1392. doi: 10.1084/jem.149.6.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. McMichael A. HLA restriction of human cytotoxic T lymphocytes specific for influenza virus. Poor recognition of virus associated with HLA A2. J Exp Med. 1978 Dec 1;148(6):1458–1467. doi: 10.1084/jem.148.6.1458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shaw S., Biddison W. E. HLA-linked genetic control of the specicity of human cytotoxic T-cell responses to influenza virus. J Exp Med. 1979 Mar 1;149(3):565–575. doi: 10.1084/jem.149.3.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shaw S., Nelson D. L., Shearer G. M. Human cytotoxic response in vitro to trinitrophenyl-modified autologous cells. I. T cell recognition of TNP in association with widely shared antigens. J Immunol. 1978 Jul;121(1):281–289. [PubMed] [Google Scholar]
  15. Yap K. L., Ada G. L. The recovery of mice from influenza A virus infection: adoptive transfer of immunity with influenza virus-specific cytotoxic T lymphocytes recognizing a common virion antigen. Scand J Immunol. 1978;8(5):413–420. doi: 10.1111/j.1365-3083.1978.tb00536.x. [DOI] [PubMed] [Google Scholar]
  16. Zinkernagel R. M., Althage A., Cooper S., Kreeb G., Klein P. A., Sefton B., Flaherty L., Stimpfling J., Shreffler D., Klein J. Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness. J Exp Med. 1978 Aug 1;148(2):592–606. doi: 10.1084/jem.148.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zinkernagel R. M., Doherty P. C. Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis. Nature. 1974 Oct 11;251(5475):547–548. doi: 10.1038/251547a0. [DOI] [PubMed] [Google Scholar]
  19. 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]

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