Prevalent role of TCR alpha-chain in the selection of the preimmune repertoire specific for a human tumor-associated self-antigen.


Autoria(s): Dietrich P.Y.; Le Gal F.A.; Dutoit V.; Pittet M.J.; Trautman L.; Zippelius A.; Cognet I.; Widmer V.; Walker P.R.; Michielin O.; Guillaume P.; Connerotte T.; Jotereau F.; Coulie P.G.; Romero P.; Cerottini J.C.; Bonneville M.; Valmori D.
Data(s)

2003

Resumo

The specificity of recognition of pMHC complexes by T lymphocytes is determined by the V regions of the TCR alpha- and beta-chains. Recent experimental evidence has suggested that Ag-specific TCR repertoires may exhibit a more V alpha- than V beta-restricted usage. Whether V alpha usage is narrowed during immune responses to Ag or if, on the contrary, restricted V alpha 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 V beta usage, but a preferential V alpha 2.1 usage. Restricted V alpha 2.1 usage was also found among single CD8(+) A2/melan-A multimer(+) thymocytes, indicating that V alpha-restricted selection takes place in the thymus. V alpha 2.1 usage, however, was independent from functional avidity of Ag recognition. Thus, interaction of the pMHC complex with selected V alpha-chains contributes to set the broad Ag specificity, as underlined by preferential binding of A2/melan-A multimers to V alpha 2.1-bearing TCRs, whereas functional outcomes result from the sum of these with other interactions between pMHC complex and TCR.

Identificador

http://serval.unil.ch/?id=serval:BIB_3C1CFD32E2B9

isbn:0022-1767[print], 0022-1767[linking]

pmid:12734356

isiid:000182758200028

Idioma(s)

en

Fonte

Journal of Immunology, vol. 170, no. 10, pp. 5103-5109

Palavras-Chave #Amino Acid Sequence; Antigens, Neoplasm; Autoantigens/genetics; Autoantigens/immunology; Cell Differentiation/genetics; Cell Differentiation/immunology; Clone Cells; Cytotoxicity, Immunologic/genetics; Epitopes, T-Lymphocyte/biosynthesis; Epitopes, T-Lymphocyte/genetics; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor/physiology; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/physiology; HLA-A2 Antigen/biosynthesis; HLA-A2 Antigen/genetics; Hematopoietic Stem Cells/immunology; Hematopoietic Stem Cells/metabolism; Humans; Melanoma/genetics; Melanoma/immunology; Molecular Sequence Data; Neoplasm Proteins/genetics; Neoplasm Proteins/immunology; RNA, Messenger/analysis; Receptors, Antigen, T-Cell, alpha-beta/biosynthesis; Receptors, Antigen, T-Cell, alpha-beta/genetics; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes, Cytotoxic/immunology; T-Lymphocytes, Cytotoxic/metabolism; Tumor Cells, Cultured
Tipo

info:eu-repo/semantics/article

article