Giuseppe
Emeritus
J Immunol. 2008 Nov 15;181(10):7407-19.
Multiple glycines in TCR alpha-chains determine clonally diverse nature of human T cell memory to influenza A virus.
Naumov YN, Naumova EN, Yassai MB, Kota K, Welsh RM, Selin LK. - Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Yuri.Naumov@umassmed.edu
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
)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.
PMID: 18981164 [PubMed - in process
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Multiple glycines in TCR alpha-chains determine clonally diverse nature of human T cell memory to influenza A virus.
Naumov YN, Naumova EN, Yassai MB, Kota K, Welsh RM, Selin LK. - Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Yuri.Naumov@umassmed.edu
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
)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.
PMID: 18981164 [PubMed - in process
-
------