Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza a virus epitopes

Shalyn C. Clute, Yuri N. Naumov, Levi B. Watkin, Nuray Aslan, John L. Sullivan, David A. Thorley-Lawson, Katherine Luzuriaga, Raymond M. Welsh, Roberto Puzone, Franco Celada, Liisa K. Selin

Research output: Contribution to journalArticlepeer-review

Abstract

Memory T cells cross-reactive with epitopes encoded by related or even unrelated viruses may alter the immune response and pathogenesis of infection by a process known as heterologous immunity. Because a challenge virus epitope may react with only a subset of the T cell repertoire in a cross-reactive epitope-specific memory pool, the vigorous cross-reactive response may be narrowly focused, or oligoclonal. We show in this article, by examining human T cell cross-reactivity between the HLA-A2-restricted influenza Avirus-encoded M158-66 epitope (GILGFVFTL) and the dissimilar Epstein-Barr virus-encoded BMLF1280-288 epitope (GLCTLVAML), that, under some conditions, heterologous immunity can lead to a significant broadening, rather than a narrowing, of the TCR repertoire. We suggest that dissimilar cross-reactive epitopes might generate a broad, rather than a narrow, T cell repertoire if there is a lack of dominant high-affinity clones; this hypothesis is supported by computer simulation.

Original languageEnglish
Pages (from-to)6753-6764
Number of pages12
JournalJournal of Immunology
Volume185
Issue number11
DOIs
Publication statusPublished - Dec 1 2010

ASJC Scopus subject areas

  • Immunology

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