Prevalent role of TCR α-chain in the selection of the preimmune repertoire specific for a human tumor-associated self-antigen

Pierre Yves Dietrich, Frédérique Anne Le Gal, Valérie Dutoit, Mikäel J. Pittet, Lydie Trautman, Alfred Zippelius, Isabelle Cognet, Valérie Widmer, Paul R. Walker, Olivier Michielin, Philippe Guillaume, Thierry Connerotte, Francine Jotereau, Pierre G. Coulie, Pedro Romero, Jean Charles Cerottini, Marc Bonneville, Danila Valmori

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The specificity of recognition of pMHC complexes by T lymphocytes is determined by the V regions of the TCR α- and β-chains. Recent experimental evidence has suggested that Ag-specific TCR repertoires may exhibit a more Vα- than Vβ-restricted usage. Whether Vα usage is narrowed during immune responses to Ag or if, on the contrary, restricted Vα usage is already defined at the early stages of TCR repertoire selection, however, has remained unexplored. Here, we analyzed V and CDR3 TCR regions of single circulating naive T cells specifically detected ex vivo and isolated with HLA-A2/melan-A peptide multimers. Similarly to what was previously observed for melan-A-specific Ag-experienced T cells, we found a relatively wide Vβ usage, but a preferential Vα 2.1 usage. Restricted Vα 2.1 usage was also found among single CD8+ A2/melan-A multimer+ thymocytes, indicating that Vα-restricted selection takes place in the thymus. Vα 2.1 usage, however, was independent from functional avidity of Ag recognition. Thus, interaction of the pMHC complex with selected Vα-chains contributes to set the broad Ag specificity, as underlined by preferential binding of A2/melan-A multimers to Vα 2.1-bearing TCRs, whereas functional outcomes result from the sum of these with other interactions between pMHC complex and TCR.

Original languageEnglish (US)
Pages (from-to)5103-5109
Number of pages7
JournalJournal of Immunology
Volume170
Issue number10
DOIs
StatePublished - May 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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