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Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale, Unité 277, Institut Pasteur, Paris, France;
Institut National de la Santé et de la Recherche Médicale, Unité 463, Institut de Biologie, Nantes, France; and
Immunotech SA, Marseilles, France
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
ß-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 Vß subsets (Vß2, Vß4, and Vß16
positive) with highly conserved TCRß complementarity-determining
region 3 (CDR3) length and junctional motifs, which represented from 11
to 98% (mean, 50%) of GLC/A2-reactive cells. While TCR ß-chains
expressed by these subsets showed limited CDR1, CDR2, and CDR3 homology
among themselves, their TCR
-chains comprised the same TCRAV region,
thus suggesting hierarchical contribution of TCR
-chain vs TCR
ß-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.
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