Dominant TCR-α requirements for a self antigen recognition in humans

Stefania Mantovani, Belinda Palermo, Silvia Garbelli, Rita Campanelli, Gioacchino Robustelli Della Cuna, Roberto Gennari, Federica Benvenuto, Erica Lantelme, Claudia Giachino

Research output: Contribution to journalArticlepeer-review

Abstract

TCR-α and -β chains are composed of somatically rearranged V, D, and J germline-encoded gene segments that confer Ag specificity. Recent crystallographic analyses revealed that TCR-α has more contacts with peptide than TCR-β, suggesting the possibility that peptide recognition predominantly relies on TCR-α. T cells specific for the self Ag Melan-A/MART-1 possess an exceptionally high precursor frequency in human histocompatibility leukocyte Ag-A2 individuals. This provided a unique situation for assessment of the structural relationship between TCR and peptide/MHC ligand at both the pre- and postimmune levels. Molecular and phenotypic analysis of many different Melan-A-specific T cell populations revealed that a structural constraint is imposed on the TCR for engagement with Melan-A peptides presented by HLA-A2, namely the highly preferential use of a particular TCRAV segment, AV2. Examination of CD8 single-positive thymocytes indicated that this preferential use in forming the Melan-A-specific TCR is mainly imposed by intrathymic positive selection. Our data demonstrate a dominant function of TCRAV2 segment in forming the TCR repertoire specific for the human self Ag Melan-A/MART-1 and support the view that Ag recognition is mediated predominantly by TCR-α.

Original languageEnglish
Pages (from-to)6253-6260
Number of pages8
JournalJournal of Immunology
Volume169
Issue number11
Publication statusPublished - Dec 1 2002

ASJC Scopus subject areas

  • Immunology

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