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

Details

Serval ID
serval:BIB_3C1CFD32E2B9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prevalent role of TCR alpha-chain in the selection of the preimmune repertoire specific for a human tumor-associated self-antigen.
Journal
Journal of Immunology
Author(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.
ISSN
0022-1767[print], 0022-1767[linking]
Publication state
Published
Issued date
2003
Volume
170
Number
10
Pages
5103-5109
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
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.
Keywords
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
Pubmed
Web of science
Create date
28/01/2008 11:14
Last modification date
20/08/2019 13:32
Usage data