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Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells

Nature volume 369, pages 407–410 (1994)Cite this article

Abstract

IT has been suggested that mutations within immunodominant cytotoxic T-lymphocyte (CTL) epitopes may be exploited by viruses to evade protective immune responses critical for clearance1–4. Viral escape could originate from passive mechanisms, such as mutations within crucial CTL epitopes, either affecting major histocompatibility complex binding or T-cell antigen receptor (TCR) recognition. Additionally, it has recently been shown that substitutions of TCR contact sites can yield analogue peptides that can still interact with the T-cell receptor but be unable to deliver a full stimulatory signal, thus inducing anergy5 or acting as an antagonist for the TCR6–8. We report here that hepatitis B virus isolates derived from two chronically infected patients display variant epitopes that act as natural TCR antagonists with the capacity to inhibit the CTL response to the wild-type epitope. During natural infection, TCR antagonist mutations of CTL epitopes could contribute to the development of viral persistence, especially if the antiviral CTL response is monospecific or the epitope is strongly immunodominant.

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Authors and Affiliations

  1. Cattedra Malattie Infettive, Università di Parma, 43100, Parma, Italy

    Antonio Bertoletti, Amalia Penna, Franco Fiaccadori & Carlo Ferrari

  2. Cytel Corporation, La Jolla, California, 92037, USA

    Alessandro Sette

  3. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, 92037, USA

    Francis V. Chisari

  4. Fondazione A. Cesalpino and I Clinica Medica, Università "La Sapienza", Roma, Italy

    Massimo Levrero

  5. Cattedra di Immunologia Clinica e Allergologia, Università di Firenze, 50134, Firenze, Italy

    Marco De Carli

Authors
  1. Antonio Bertoletti
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  2. Alessandro Sette
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  3. Francis V. Chisari
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  4. Amalia Penna
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  5. Massimo Levrero
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  6. Marco De Carli
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  7. Franco Fiaccadori
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  8. Carlo Ferrari
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Bertoletti, A., Sette, A., Chisari, F. et al. Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature 369, 407–410 (1994). https://doi.org/10.1038/369407a0

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