Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2009

Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope.

Résumé

Protective T cell responses elicited along chronic human CMV (HCMV) infections are sometimes dominated by CD8 T cell clones bearing highly related or identical public TCR in unrelated individuals. To understand the principles that guide emergence of these public T cell responses, we have performed structural, biophysical, and functional analyses of an immunodominant public TCR (RA14) directed against a major HLA-A*0201-restricted HCMV Ag (pp65(495-503)) and selected in vivo from a diverse repertoire after chronic stimulations. Unlike the two immunodominant public TCRs crystallized so far, which focused on one peptide hotspot, the HCMV-specific RA14 TCR interacts with the full array of available peptide residues. The conservation of some peptide-MHC complex-contacting amino acids by lower-affinity TCRs suggests a shared TCR-peptide-MHC complex docking mode and supports an Ag-driven selection of optimal TCRs. Therefore, the emergence of a public TCR of an oligoclonal Ag-specific response after repeated viral stimulations is based on a receptor displaying a high structural complementarity with the entire peptide and focusing on three peptide hotspots. This highlights key parameters underlying the selection of a protective T cell response against HCMV infection, which remains a major health issue in patients undergoing bone marrow transplantation.

Domaines

Immunologie

Dates et versions

hal-00432094 , version 1 (13-11-2009)

Identifiants

Citer

Stéphanie Gras, Xavier Saulquin, Jean-Baptiste Reiser, Emilie Debeaupuis, Klara Echasserieau, et al.. Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope.. Journal of Immunology, 2009, 183 (1), pp.430-7. ⟨10.4049/jimmunol.0900556⟩. ⟨hal-00432094⟩
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