TY - JOUR
T1 - Prevalent role of TCR α-chain in the selection of the preimmune repertoire specific for a human tumor-associated self-antigen
AU - Dietrich, Pierre Yves
AU - Le Gal, Frédérique Anne
AU - Dutoit, Valérie
AU - Pittet, Mikäel J.
AU - Trautman, Lydie
AU - Zippelius, Alfred
AU - Cognet, Isabelle
AU - Widmer, Valérie
AU - Walker, Paul R.
AU - Michielin, Olivier
AU - Guillaume, Philippe
AU - Connerotte, Thierry
AU - Jotereau, Francine
AU - Coulie, Pierre G.
AU - Romero, Pedro
AU - Cerottini, Jean Charles
AU - Bonneville, Marc
AU - Valmori, Danila
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2003/5/15
Y1 - 2003/5/15
N2 - The specificity of recognition of pMHC complexes by T lymphocytes is determined by the V regions of the TCR α- and β-chains. Recent experimental evidence has suggested that Ag-specific TCR repertoires may exhibit a more Vα- than Vβ-restricted usage. Whether Vα usage is narrowed during immune responses to Ag or if, on the contrary, restricted Vα usage is already defined at the early stages of TCR repertoire selection, however, has remained unexplored. Here, we analyzed V and CDR3 TCR regions of single circulating naive T cells specifically detected ex vivo and isolated with HLA-A2/melan-A peptide multimers. Similarly to what was previously observed for melan-A-specific Ag-experienced T cells, we found a relatively wide Vβ usage, but a preferential Vα 2.1 usage. Restricted Vα 2.1 usage was also found among single CD8+ A2/melan-A multimer+ thymocytes, indicating that Vα-restricted selection takes place in the thymus. Vα 2.1 usage, however, was independent from functional avidity of Ag recognition. Thus, interaction of the pMHC complex with selected Vα-chains contributes to set the broad Ag specificity, as underlined by preferential binding of A2/melan-A multimers to Vα 2.1-bearing TCRs, whereas functional outcomes result from the sum of these with other interactions between pMHC complex and TCR.
AB - The specificity of recognition of pMHC complexes by T lymphocytes is determined by the V regions of the TCR α- and β-chains. Recent experimental evidence has suggested that Ag-specific TCR repertoires may exhibit a more Vα- than Vβ-restricted usage. Whether Vα usage is narrowed during immune responses to Ag or if, on the contrary, restricted Vα usage is already defined at the early stages of TCR repertoire selection, however, has remained unexplored. Here, we analyzed V and CDR3 TCR regions of single circulating naive T cells specifically detected ex vivo and isolated with HLA-A2/melan-A peptide multimers. Similarly to what was previously observed for melan-A-specific Ag-experienced T cells, we found a relatively wide Vβ usage, but a preferential Vα 2.1 usage. Restricted Vα 2.1 usage was also found among single CD8+ A2/melan-A multimer+ thymocytes, indicating that Vα-restricted selection takes place in the thymus. Vα 2.1 usage, however, was independent from functional avidity of Ag recognition. Thus, interaction of the pMHC complex with selected Vα-chains contributes to set the broad Ag specificity, as underlined by preferential binding of A2/melan-A multimers to Vα 2.1-bearing TCRs, whereas functional outcomes result from the sum of these with other interactions between pMHC complex and TCR.
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U2 - 10.4049/jimmunol.170.10.5103
DO - 10.4049/jimmunol.170.10.5103
M3 - Article
C2 - 12734356
AN - SCOPUS:0037546979
SN - 0022-1767
VL - 170
SP - 5103
EP - 5109
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -