Frequent contribution of T cell clonotypes with public TCR features to the chronic response against a dominant EBV-derived epitope: Application to direct detection of their molecular imprint on the human peripheral T cell repertoire

A. Lim, L. Trautmann, M. A. Peyrat, C. Couedel, F. Davodeau, F. Romagne, P. Kourilsky, M. Bonneville

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

In an attempt to provide a global picture of the TCR repertoire diversity of a chronic T cell response against a common Ag, we performed an extensive TCR analysis of cells reactive against a dominant HLA-A2-restricted EBV epitope (hereafter referred to as GLC/A2), obtained after sorting PBL or synovial fluid lymphocytes from EBV-seropositive individuals using MHC/peptide multimers. Although TCR β-chain diversity of GLC/A2+ T cells was extensive and varied greatly from one donor to another, we identified in most cell lines several recurrent Vβ subsets (Vβ2, Vβ4, and Vβ16 positive) with highly conserved TCRβ complementarity-determining region 3 (CDR3) length and junctional motifs, which represented from 11 to 98% (mean, 50%) of GLC/A2-reactive cells. While TCR β-chains expressed by these subsets showed limited CDR1, CDR2, and CDR3 homology among themselves, their TCR α- chains comprised the same TCRAV region, thus suggesting hierarchical contribution of TCR α-chain vs TCR β-chain CDR to recognition of this particular MHC/peptide complex. The common occurrence of T cell clonotypes with public TCR features within GLC/A2-specific T cells allowed their direct detection within unsorted PBL using ad hoc clonotypic primers. These results, which suggest an unexpectedly high contribution of public clonotypes to the TCR repertoire against a dominant epitope, have several implications for the follow-up and modulation of T cell-mediated immunity.

Original languageEnglish (US)
Pages (from-to)2001-2011
Number of pages11
JournalJournal of Immunology
Volume165
Issue number4
DOIs
StatePublished - Aug 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Frequent contribution of T cell clonotypes with public TCR features to the chronic response against a dominant EBV-derived epitope: Application to direct detection of their molecular imprint on the human peripheral T cell repertoire'. Together they form a unique fingerprint.

Cite this