Multiple glycines in TCR α-chains determine clonally diverse nature of human T cell memory to influenza A virus

Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
The Journal of Immunology (Impact Factor: 4.92). 12/2008; 181(10):7407-19. DOI: 10.4049/jimmunol.181.10.7407
Source: PubMed


Detailed assessment of how the structural properties of T cell receptors affect clonal repertoires of Ag-specific cells is a prerequisite for a better understanding of human antiviral immunity. Herein we examine the alpha TCR repertoires of CD8 T cells reactive against the influenza A viral epitope M1(58-66), restricted by HLA-A2.1. Using molecular cloning, we systematically studied the impact of alpha-chain usage in the formation of T cell memory and revealed that M1(58-66)-specific, clonally diverse VB19 T cells express alpha-chains encoded by multiple AV genes with different CDR3 sizes. A unique feature of these alpha TCRs was the presence of CDR3 fitting to an AGA(G(n))GG-like amino acid motif. This pattern was consistent over time and among different individuals. Further molecular assessment of human CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes led to the conclusion that the poly-Gly/Ala runs in CDR3alpha were a property of immune, but not naive, repertoires and could be attributed to influenza exposure. Repertoires of T cell memory are discussed in the context of clonal diversity, where poly-Gly/Ala runs in the CDR3 of alpha- and beta-chains might provide high levels of TCR flexibility during Ag recognition while gene-encoded CDR1 and CDR2 contribute to the fine specificity of the TCR-peptide MHC interaction.

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Available from: Elena N Naumova, Oct 01, 2015
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    • "That the initial antiviral response in humans is maintained for many years in latent virus infected individuals was reported by Klarenbeek et al. [33]. In addition, Naumov et al. examined the TCR repertoire of CD8 T cells reactive against the influenza A viral epitope M1 (58–66) [34]. These studies were carried out usually using the high throughput sequencing (HTS), flow cytometry or molecular cloning techniques. "
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