Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza A virus epitopes
Biochemistry & Molecular Pharmacology
Department of Pathology; Department of Pediatrics; Program in Molecular Medicine
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Immunol. 2010 Dec 1;185(11):6753-64. Epub 2010 Nov 3. doi: 10.4049/jimmunol.1000812
Journal of immunology (Baltimore, Md. : 1950)
Clute, Shalyn Catherine; Naumov, Yuri N.; Watkin, Levi B.; Aslan, Nuray; Sullivan, John L.; Thorley-Lawson, David A.; Luzuriaga, Katherine; Welsh, Raymond M.; Puzone, Roberto; Celada, Franco; and Selin, Liisa K., "Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza A virus epitopes" (2010). GSBS Student Publications. 1777.