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

J Immunol. 2008 Nov 15;181(10):7407-19. doi: 10.4049/jimmunol.181.10.7407.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Amino Acid Motifs / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Clone Cells
  • Flow Cytometry
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor*
  • Genes, T-Cell Receptor alpha
  • Glycine / immunology*
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunologic Memory*
  • Infant
  • Influenza A virus / immunology
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Viral Matrix Proteins / immunology*

Substances

  • HLA-A2 Antigen
  • M1 protein, Influenza A virus
  • Receptors, Antigen, T-Cell, alpha-beta
  • Viral Matrix Proteins
  • Glycine