Antiviral T-Cell Memory?

  • R. M. Zinkernagel
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 159)


Generally, it is accepted that immunological memory exists at both the B- and the T-cell level (reviewed in Katz 1977). It has been known for more than 100 years that the persistence of high antibody titers (Fig. 1) can be lifelong after viral infections and that delayed-type hypersensitivity can be demonstrated for a long time by challenging with a protein antigen after prior infection with tubercle bacilli. The concept of providing protection from disease by vaccination depends entirely on the existence of immunological memory. Although evidence for B-cell memory is abundant (Katz 1977), it is not clear whether it is maintained by means of (a) persistence of antigen, (b) continuous exposure to cross-reactive “natural” environmental antigen, or (c) the existence of true memory B cells.


Influenza Virus Vesicular Stomatitis Virus Immunological Memory Challenge Infection Major Surface Glycoprotein 
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. Andrew ME, Coupar BEH, Boyle DB, Ada GL (1987) The roles of influenza virus haemagglutinin and nucleoprotein in protection: analysis using vaccinia virus recombinants. Scand J Immunol 25: 21–28PubMedCrossRefGoogle Scholar
  2. Anonymous (1986) Reinfections with influenza. Lancet ii: 372–374Google Scholar
  3. Babbitt BP, Allen PM, Matsueda G, Haber E, Unanue ER (1985) Binding of immunogenic peptides to Ia histocompatibility molecules. Nature 317: 359–360PubMedCrossRefGoogle Scholar
  4. Berzofsky JA (1983) T-B reciprocity: an la-restricted epitopes-specific circuit regulating T cell-B cell interaction and antibody specificity. Surv Immunol Res 2: 223–230PubMedGoogle Scholar
  5. Blanden RV (1974) T cell response to viral and bacterial infection. Transplant Rev 19: 56–84PubMedGoogle Scholar
  6. Blanden RV, Kees U, Dunlop MBC (1977) In vitro primary induction of cytotoxic T cells against virus-infected syngeneic cells. J Immunol Methods 16: 73–89PubMedCrossRefGoogle Scholar
  7. Bricker BJ, Snyder RM, Fox JW, Volk WA, Wagner RR (1987) Monoclonal antibodies to the glycoprotein of vesicular stomatitis virus (New Jersey Serotype): a method for preliminary mapping of epitopes. Virology 161: 533–540PubMedCrossRefGoogle Scholar
  8. Buus S, Sette A, Colon SM, Miles C, Grey HM (1987) The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science 235: 1353–1358PubMedCrossRefGoogle Scholar
  9. Charan S, Zinkernagel RM (1986) Antibody mediated suppression of secondary IgM response in nude mice against vesicular stomatitis virus. J Immunol 136: 3057–3061PubMedGoogle Scholar
  10. Charan S, Roost HP, Hengartner H, Zinkernagel RM (1989) Analysis of the kinetics of antiviral T help in vivo (manuscript in preparation)Google Scholar
  11. Dietzschold B, Schneider LG, Cox JH (1974) Serological characterization of the three major proteins of vesicular stomatitis virus. J Virol 14: 1–7PubMedGoogle Scholar
  12. Doherty PC, Zinkernagel RM (1974) T cell-mediated immunopathology in viral infection. Transplant Rev 19: 89–120PubMedGoogle Scholar
  13. Doherty PC, Effros RB, Bennink J (1977) Heterogeneity of the cytotoxic response of thymus-derived lymphocytes after immunization with influenza viruses. Proc Natl Acad Sci USA 74: 1209–1213PubMedCrossRefGoogle Scholar
  14. Effors RB, Bennink J, Doherty PC (1978) Characteristics of secondary cytotoxic T cell responses in mice infected with influenza A virus. Cell Immunol 36: 345–353CrossRefGoogle Scholar
  15. Fazekas de St. Groth S (1981) The joint evolution of antigens and antibodies in the immune system. In: Steinberg CM, Lefkovits I (eds) The immune system, Vol. I. Karger, Basel, pp 155–168Google Scholar
  16. Gallione CJ, Rose JK (1983) Nucleotide sequence of a cDNA clone encoding the entire glycoprotein from the New Jersey serotype of vesicular stomatitis virus. J Virol 46: 162–169PubMedGoogle Scholar
  17. Germain RN (1986) The ins and outs of antigen processing and presentation. Nature 322: 687–689PubMedCrossRefGoogle Scholar
  18. Guillet JG, Lai M-Z, Briner TJ, Buus S, Sette A, Grey HM, Smith JA, Gefter ML (1987) Immunological self, nonself discrimination. Science 235: 865–870PubMedCrossRefGoogle Scholar
  19. Gupta SC, Hengartner H, Zinkernagel RM (1986) Primary antibody responses to a well-defined and unique hapten are not enhanced by preimmunization with carrier: analysis in a viral model. Proc Natl Acad Sci USA 83: 2604–2608PubMedCrossRefGoogle Scholar
  20. Hackett CJ, Dietzschold B, Gerhard W, Ghrist B, Knorr R, Gillessen D, Melchers F (1983) Influenza virus site recognized by a murine helper T cell specific for H1 strains: localisation to a nine amino acid sequence in the hemagglutinin molecule. J Exp Med 158: 294–302PubMedCrossRefGoogle Scholar
  21. Jungi TW (1980) Immunological memory to Listeria monocytogenes in rodents: evidence for protective T lymphocytes outside the recirculating lymphocyte pool. J Reticuloendothel Soc 28:405–417PubMedGoogle Scholar
  22. Katz DH (1977) Lymphocyte differentiation, recognition and regulation. Academic, New YorkGoogle Scholar
  23. Katz DH, Benacerraf B (1972) The regulatory influence of activated T cells on B cell responses to antigens. Adv Immunol 15: 1–94PubMedCrossRefGoogle Scholar
  24. Kees U, Krammer PH (1984) Most influenza A virus specific memory cytotoxic T lymphocytes react with antigenic epitopes associated with internal virus determinants. J Exp Med 159: 365–377PubMedCrossRefGoogle Scholar
  25. Lamb JR, Eckles DD, Lake P, Woody JN, Green N (1982) Human T-cell clones recognize chemically synthesized peptides of influenza hemagglutinin. Nature 300: 66–69PubMedCrossRefGoogle Scholar
  26. Lefrançois L, Lyles DS (1982a) The interaction of antibody with the major surface glycoprotein of vesicular stomatitis virus. II. Monoclonal antibodies to non-neutralizing and cross-reactive epitopes of Indiana and New Jersey serotypes. Virology 121: 168–174PubMedCrossRefGoogle Scholar
  27. Lefrançois L, Lyles DS (1982b) The interaction of antibody with the major surface glycoprotein of vesicular stomatitis virus. I. Analysis of neutralizing epitopes with monoclonal antibodies. Virology 121: 157–167PubMedCrossRefGoogle Scholar
  28. Mackaness GB (1969) The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med 129: 973–992PubMedCrossRefGoogle Scholar
  29. Manca F, Kunkl A, Fenoglio D, Fowler A, Sercarz E, Celada F (1985) Constraints in T-B cooperation related to epitope topology on E. coli β-galactosidase. - I. The fine specificity of T cells dictates the fine specificity of antibodies directed to conformation-dependent determinants. Eur J Immunol 15: 345–350PubMedCrossRefGoogle Scholar
  30. McMichael AJ, Gotch FM, Dongworth DW, Clark A, Potter C (1983) Declining T cell immunity to influenza 1977–1982. Lancet ii: 762–764CrossRefGoogle Scholar
  31. Mullbacher A, Marshall ID, Blanden RV (1981) Cross-reactive cytotoxic T cell to alphavirus infection. Scand J Immunol 10: 291–297CrossRefGoogle Scholar
  32. Pirquet C (1907) Von klinischen Studien über Vakzination und vakzinale Allergie. Denticke, F LeipzigGoogle Scholar
  33. Plata F, Cerottini JC, Brunner KT (1975) Primary and secondary in vitro generation of cytolytic T lymphocytes in the murine sarcoma virus system. Eur J Immunol 5: 227–233PubMedCrossRefGoogle Scholar
  34. Rock KL, Benacerraf B (1983) Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. J Exp Med 157: 1618–1634PubMedCrossRefGoogle Scholar
  35. Rosenthal KL, Zinkernagel RM (1980) Cross-reactive cytotoxic T cells to serologically distinct vesicular stomatitis viruses. J Immunol 124: 2301–2308PubMedGoogle Scholar
  36. Russell SM, Liew FY (1980) Cell cooperation in antibody responses to influenza virus. I. Priming of helper T cells by internal components of the virion. Eurr J Immunol. 10: 791–796CrossRefGoogle Scholar
  37. Sprent J, Miller JFAP (1976) Effect of recent antigen priming on adoptive immune responses. III. Antigen-induced selective recruitment of subsets of recirculating lymphocytes reactive to H-2 determinants. J Exp Med 143: 585–598PubMedCrossRefGoogle Scholar
  38. Swain SL (1981) Significance of Lyt phenotypes: Lyt-2 antibodies block activities of T cells that recognize class I major histocompatibility complex antigens regardless of their function. Proc Natl Acad Sci USA 78: 7101–7105PubMedCrossRefGoogle Scholar
  39. Thomas DB, Hackett CJ, Askonas BA (1972) Evidence for two T-helper populations with distinct specificity in the humoral response to influenza A viruses. Immunology 47: 429–436Google Scholar
  40. Townsend ARM, McMichael AJ (1985) Specificity of cytotoxic T lymphocytes stimulated with influenza virus. Studies in mice and humans. Prog Allergy 36: 10–43PubMedGoogle Scholar
  41. Townsend ARM, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ (1986) The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44: 959–968PubMedCrossRefGoogle Scholar
  42. Wagner RR (1975) Reproduction of rhabdoviruses: composite model of infection. Virology 4:41Google Scholar
  43. Wolcott JA, Wust CJ, Brown A (1982) Immunization with one alphavirus cross-primes cellular and humoral immune responses to a second alphavirus. J Immunol 129: 1267–1271PubMedGoogle Scholar
  44. Yewdell JW, Bennink JR, Smith GL, Moss B (1985) Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus nucleoprotein is a major target antigen for cross- reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci USA 82: 1785–1789PubMedCrossRefGoogle Scholar
  45. Yewdell JW, Bennink JR, Mackett M, Lefrançois L, Lyles DS, Moss B (1986) Recognition of cloned vesicular stomatitis virus internal and external gene products by cytotoxic T lymphocytes. J Exp Med 163: 1529–1538PubMedCrossRefGoogle Scholar
  46. Zinkernagel RM (1979) Heterogeneization and MHC restricted T cells. In: Kobayashi H (ed) Immunological zenogenization of tumor cells. University Park Press, Baltimore, pp 181–184Google Scholar
  47. Zinkernagel RM, Rosenthal KL (1981) Experiments and speculation on antiviral specificity of T and B cells. Immunol Rev 58: 131–155PubMedCrossRefGoogle Scholar
  48. Zinkernagel RM, Hengartner H, Stitz L (1985) On the role of viruses in the evolution of immune responses. Br Med Bull 41: 92–97PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • R. M. Zinkernagel
    • 1
  1. 1.Institute of PathologyUniversity HospitalZürichSwitzerland

Personalised recommendations