Multiple glycines in TCR alpha-chains determine clonally diverse nature of human T cell memory to influenza A virus.
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.
Naumov
Yuri N
YN
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Yuri.Naumov@umassmed.edu
Naumova
Elena N
EN
Yassai
Maryam B
MB
Kota
Kalyani
K
Welsh
Raymond M
RM
Selin
Liisa K
LK
D000328:Adult; D020816:Amino Acid Motifs / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D005434:Flow Cytometry; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha; D005998:Glycine / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D009980:Influenza A virus / Q000276:immunology; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014763:Viral Matrix Proteins / Q000276:immunology*
D015789:HLA-A2 Antigen; C488936:M1 protein, Influenza A virus; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014763:Viral Matrix Proteins; D005998:Glycine