Multiple Glycines in TCR α-Chains Determine Clonally Diverse Nature of Human T Cell Memory to Influenza A Virus
Multiple Glycines in TCR α-Chains Determine Clonally Diverse Nature of Human T Cell Memory to Influenza A Virus
复制标题
DOI：
10.4049/jimmunol.181.10.7407
复制
发表时间：
2008-11-15
影响因子：
4.4
通讯作者：
Selin, Liisa K.
中科院分区：
文献类型：
--
作者：
Naumov, Yuri N.;Naumova, Elena N.;Selin, Liisa K.
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(58-56), 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(58-56)-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 CDR3 alpha 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. The Journal of Immunology, 2008,181: 7407-7419.
