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The Journal of Immunology, 00, 165: 2001-2011.
Copyright © 00 by The American Association of Immunologists

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 Repertoire1

Annick Lim*, Lydie Trautmann{dagger}, Marie-Alix Peyrat{dagger}, Chrystelle Couedel{dagger}, François Davodeau{dagger}, François Romagné{ddagger}, Philippe Kourilsky* and Marc Bonneville2,{dagger}

* Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale, Unité 277, Institut Pasteur, Paris, France; {dagger} Institut National de la Santé et de la Recherche Médicale, Unité 463, Institut de Biologie, Nantes, France; and {ddagger} 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 {alpha}-chains comprised the same TCRAV region, thus suggesting hierarchical contribution of TCR {alpha}-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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