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J Immunol. 2010 Dec 1;185(11):6753-64. doi: 10.4049/jimmunol.1000812. Epub 2010 Nov 3.

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

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  • 1Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.


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 A virus-encoded M1(58-66) epitope (GILGFVFTL) and the dissimilar Epstein-Barr virus-encoded BMLF1(280-288) 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.

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