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Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes

Author

Listed:
  • Paul Klenerman

    (Institute for Experimental Immunology, University Hospital)

  • Rolf M. Zinkernagel

    (Institute for Experimental Immunology, University Hospital)

Abstract

Some viruses, including human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in humans, and lymphocytic choriomeningitis virus (LCMV) in mice, are initially controlled by cytotoxic T lymphocytes (CTLs), but may subsequently escape through mutation of the relevant T-cell epitope1,2,3. Some of these mutations preserve the normal binding to major histocompatibility complex class I molecules, but present an altered surface to the T-cell antigen receptor4,5. The exact role of these so-called altered peptide ligands in vivo is not clear. Here we report that mice primed with LCMV-WE strain respond to a subsequent infection by WE-derived CTL epitope variants with a CTL response directed against the initial epitope rather than against the new variant epitope. This phenomenon of ‘original antigenic sin’ was initially described in influenza6,7,8 and is an asymmetric pattern of protective antibody crossreactivity determined by exposure to previously existing strains, which may therefore extend to some CTL responses. Original antigenic sin by CTL leads to impaired clearance of variant viruses infecting the same individual and so may enhance the immune escape of mutant viruses evolving in an individual host.

Suggested Citation

  • Paul Klenerman & Rolf M. Zinkernagel, 1998. "Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes," Nature, Nature, vol. 394(6692), pages 482-485, July.
  • Handle: RePEc:nat:nature:v:394:y:1998:i:6692:d:10.1038_28860
    DOI: 10.1038/28860
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    Cited by:

    1. Park, Jeong-Man & Deem, Michael W., 2004. "Correlations in the T-cell response to altered peptide ligands," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 341(C), pages 455-470.
    2. Vitaly V Ganusov & Sergei S Pilyugin & Rafi Ahmed & Rustom Antia, 2006. "How Does Cross-Reactive Stimulation Affect the Longevity of CD8+ T Cell Memory?," PLOS Computational Biology, Public Library of Science, vol. 2(6), pages 1-10, June.

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