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 journalArticle

31 Citations (Scopus)

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

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Orthomyxoviridae
Epitopes
Heterologous Immunity
T-Lymphocytes
Viruses
HLA-A2 Antigen
T-Lymphocyte Subsets
Human Herpesvirus 4
Computer Simulation
Human Influenza
Clone Cells
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Clute, S. C., Naumov, Y. N., Watkin, L. B., Aslan, N., Sullivan, J. L., Thorley-Lawson, D. A., ... Selin, L. K. (2010). Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza a virus epitopes. Journal of Immunology, 185(11), 6753-6764. https://doi.org/10.4049/jimmunol.1000812

Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza a virus epitopes. / Clute, Shalyn C.; Naumov, Yuri N.; Watkin, Levi B.; Aslan, Nuray; Sullivan, John L.; Thorley-Lawson, David A.; Luzuriaga, Katherine; Welsh, Raymond M.; Puzone, Roberto; Celada, Franco; Selin, Liisa K.

In: Journal of Immunology, Vol. 185, No. 11, 01.12.2010, p. 6753-6764.

Research output: Contribution to journalArticle

Clute, SC, Naumov, YN, Watkin, LB, Aslan, N, Sullivan, JL, Thorley-Lawson, DA, Luzuriaga, K, Welsh, RM, Puzone, R, Celada, F & Selin, LK 2010, 'Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza a virus epitopes', Journal of Immunology, vol. 185, no. 11, pp. 6753-6764. https://doi.org/10.4049/jimmunol.1000812
Clute SC, Naumov YN, Watkin LB, Aslan N, Sullivan JL, Thorley-Lawson DA et al. Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza a virus epitopes. Journal of Immunology. 2010 Dec 1;185(11):6753-6764. https://doi.org/10.4049/jimmunol.1000812
Clute, Shalyn C. ; Naumov, Yuri N. ; Watkin, Levi B. ; Aslan, Nuray ; Sullivan, John L. ; Thorley-Lawson, David A. ; Luzuriaga, Katherine ; Welsh, Raymond M. ; Puzone, Roberto ; Celada, Franco ; Selin, Liisa K. / Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza a virus epitopes. In: Journal of Immunology. 2010 ; Vol. 185, No. 11. pp. 6753-6764.
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