Recognition of Influenza A Virus by Human Cytotoxic T Lymphocytes

  • Andrew J. McMichael
  • Frances M. Gotch
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 257)


Cytotoxic T lymphocytes (CTL) are an important component of the immune system carrying the CD8 surface glycoprotein and forming a significant part of the total lymphoid population. The role of CTL appears to be to kill cells of the body that differ from normal and this occurs during infection with intracellular parasites, particularly viruses. It is likely that CTL have evolved as a major defence mechanism against virus infections. CTL are detected in vitro by their ability to kill infected target cells that are labelled with chromium-51. There is evidence that CTL lyse infected cells in vivo (1) and they may also act by releasing lymphokines such as Interferon-Gamma (2). When infected cells are killed they can no longer replicate new virus particles, and if the cell is already doomed this is an effective way of controlling a virus infection. However the constraints on CTL antigen receptors preclude them from recognising and neutralising virus particules directly. The natural role of CTL therefore is likely to be quite distinct from that of the antibody response.


Major Histocompatibility Complex Influenza Virus Major Histocompatibility Complex Class Major Histocompatibility Complex Molecule Major Histocompatibility Complex Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    R.M. Zinkernagel, E. Haenseler, T. Leist, A. Cerny, H. Hengartner and A.Althage. T cell mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 5lCr release assay? J.Exp.Med. 164:1075.(1986).PubMedCrossRefGoogle Scholar
  2. 2.
    A.G. Morris, Y.L. Lin and B.A. Askonas. Immune interferon release when a cloned cytotoxic T cell line meets its correct influenza infected target cells. Nature 295:150. (1982).PubMedCrossRefGoogle Scholar
  3. 3.
    K.L. Yap, G.L. Ada, I.F.C. McKenzie. Transfer of specific cytotoxic T lymphocytes protect mice inoculated with influenza virus. Nature 273:238. (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    Y.L. Lin and B.A. Askonas. Biological properties of an influenza A virus specific killer T cell clone. J.Exp.Med. 154:225. (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    K.L. Yap and G.L. Ada. Cytotoxic T cells in the lungs of mice infected with influenza A virus. Scand.J.Immunol. 7:73 (1978).PubMedCrossRefGoogle Scholar
  6. 6.
    A.J. McMichael,F.M. Gotch, G.R. Noble and P.A.S. Beare. Cytotoxic T-cell immunity to influenza. N.Engl.J.Med. 309:13. (1983).PubMedCrossRefGoogle Scholar
  7. 7.
    M.A. Wells, P. Albrecht and F.A. Ennis. Recovery from a viral respiratory tract infection.I.Influenza pneumonia in normal and T deficient mice. J.Immunol. 126:1036. (1981).PubMedGoogle Scholar
  8. 8.
    M.A. Wells, F.A. Ennis and P. Albrecht. Recovery from a viral respiratory tract infection.II.Passive transfer of immune spleen cells to mice with influenza pneumonia. J.Immunol. 126:1042. (1981).PubMedGoogle Scholar
  9. 9.
    R.M. Zinkernagel and P.C. Doherty. H-2 compatibility requirement for T-cell mediated lysis of target cells infected with lymphocytic choriomeningitis virus. J.Exp.Med. 141:1427. (1975).PubMedCrossRefGoogle Scholar
  10. 10.
    H.J. Zweerink, S.A. Courtneidge, J.J. Skehel, M.J. Crumpton and B.A. Askonas. Cytotoxic T cells kill influenza virus-infected cells but do not distinguish between serologically distinct type A viruses. Nature 267:354. (1977).PubMedCrossRefGoogle Scholar
  11. 11.
    T.J. Braciale. Immunologic recognition of influenza-virus infected cells. Generation of virus strain specific and cross reactive subpopulations of cytotoxic T-cells in the response to type A influenza viruese of different subtypes. Cell.Immunol. 33:423. (1977).PubMedCrossRefGoogle Scholar
  12. 12.
    A.J. McMichael, A.Ting, H.J. Zweerink and B.A. Askonas. HLA restriction of cell mediated lysis of influenza virus infected human cells. Nature 270:524. (1977=.PubMedCrossRefGoogle Scholar
  13. 13.
    Z. Dembic, W.Haas, S. Weiss et al. Transfer of specificity of murine alpha and beta T-cell receptor genes. Nature 320:232. (1986).PubMedCrossRefGoogle Scholar
  14. 14.
    T.J. Braciale, V.L. Braciale, T.J. Henkel, J. Sambrook and M-J. Gething. Cytotoxic T lymphocyte recognition of the influenza haemagglutinin gene product expressed by DNA-mediated gene transfer. J.Exp.Med. 159:341. (1984).PubMedCrossRefGoogle Scholar
  15. 15.
    A.R.M. Townsend, A.J. McMichael, N.P. Carter, J.A. Huddleston and G.G. Brownlee. Cytotoxic T cell recognition of the influenza nucleoprotein and haemagglutinin expressed in transfected mouse L cells. Cell. 39:13.(1984).PubMedCrossRefGoogle Scholar
  16. 16.
    A.R.M. Townsend and J.J. Skehel. Influenza A specific cytotoxic T-cell clones that do not recognise viral glycoproteins. Nature 300:655.(1982)PubMedCrossRefGoogle Scholar
  17. 17.
    J.R. Bennink, J.W. Yewdell, G.L. Smith, C. Moller and B. Moss. Recombinant vaccinia virus primes and stimulates influenza haemagglu-tinin-specific cytotoxic T cells. Nature 311:578. (1984).PubMedCrossRefGoogle Scholar
  18. 18.
    J.W. Yewdell, J.R. Bennink, G.L. Smith and B. Moss. Influenza A virus nucleoprotein is a major target antigen for cross reactive antiinfluenza A virus cytotoxic T lymphocytes. P.N.A.S. (USA) 82:1785. (1985)CrossRefGoogle Scholar
  19. 19.
    F.M. Gotch, A.J. McMichael, G.Smith and B. Moss. Identification of viral molecules recognized by influenza-specific human cytotoxic T lymphocytes. J.Exp.Med. 165:408. (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    R.H. Schwartz. T lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Ann.Rev.Immunol. 3:237. (1985).CrossRefGoogle Scholar
  21. 21.
    A.R.M. Townsend, F.M. Gotch and J. Davey. Cytotoxic T-cells recognise fragments of the influenza nucleoprotein. Cell 42:457. (1985).PubMedCrossRefGoogle Scholar
  22. 22.
    A.R.M. Townsend, J. Bastin, K. Gould and G.G. Brownlee. Cytotoxic T lymphocytes recognise influenza haemagglutinin that lacks a signal sequence. Nature 234:575. (1986).CrossRefGoogle Scholar
  23. 23.
    A.R.M. Townsend, J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith and A.J. McMichael. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44:959. (1986).PubMedCrossRefGoogle Scholar
  24. 24.
    J. Bastin, J. Rothbard, J. Davey, I. Jones and A. Townsend. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I restricted cytotoxic T lymphocytes. J.Exp.Med. 165:1508. (1987).PubMedCrossRefGoogle Scholar
  25. 25.
    A.J. McMichael, F.M. Gotch, and J. Rothbard. HLA B37 determines an influenza A virus nucleoprotein epitope recognized by cytotoxic T lymphocytes. J.Exp.Med. 164:1397. (1986).PubMedCrossRefGoogle Scholar
  26. 26.
    F. Gotch, J. Rothbard, J. Howland, A. Townsend and A. McMichael. Cytotoxic T lymphocytes recognise a fragment of influenza virus matrix protein in association with HLA-A2. Nature 326:881. (1987).PubMedCrossRefGoogle Scholar
  27. 27.
    P.J. Bjorkman, M.A. Saper, B. Samraoui, W.S. Bennett, J.L. Strominger and D.C. Wiley. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 329:511. (1987).Google Scholar
  28. 28.
    P.J. Bjorkman, M.A. Saper, B. Samraoui, W.S. Bennett, J.L. Strominger and D.C. Wiley. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 329:512. (1987).PubMedCrossRefGoogle Scholar
  29. 29.
    A.J. McMichael, F. Gotch, J. Santos-Aguado and J. Strominger. The effect of mutations and variations of HLA-A2 on recognition of a virus peptide epitope by cytotoxic T lymphocytes. P.N.A.S. (USA). In press. (1988).Google Scholar
  30. 30.
    F. Gotch, A. McMichael and J. Rothbard. Recognition of influenza A matrix protein by HLA A2 restricted cytotoxic T lymphocytes. Use of analogues to orientate the matrix peptide in the HLA A2 binding site. J.Exp.Med. In press (1988).Google Scholar
  31. 31.
    S. Buus, A. Sette, S.M. Colon, D.M. Jenis and H.M. Grey. Isolation and characterization of antigen-la complexes involved in T cell recognition. Cell 47:1071. (1986).PubMedCrossRefGoogle Scholar
  32. 32.
    H. Bodmer, J. Bastin, B. Askonas and A. Townsend. Influenza specific cytotoxic T cell recognition is inhibited by peptides unrelated in both sequence and MHC restriction. Immunology. In press (1988).Google Scholar
  33. 33.
    A. Hershko and A. Ciechanover. The ubiquitin pathway for the degradation of intracellular proteins. Prog.Nucleic Acid.Res.Mol. Biol. 33:19 (1986).PubMedCrossRefGoogle Scholar
  34. 34.
    F. Carbone. M. Moore, J. Sheil and M. Bevan. Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. J. Exp.Med. 167:1767. (1988).PubMedCrossRefGoogle Scholar
  35. 35.
    H. Bodmer, F. Gotch and A.McMichael. Cross-restricted T cells reveal low responder allele due to processing of viral antigens. Submitted. (1988).Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Andrew J. McMichael
    • 1
  • Frances M. Gotch
    • 1
  1. 1.Institute of Molecular Medicine John Radcliffe HospitalUniversity of OxfordOxfordUK

Personalised recommendations