Hierarchal utilization of different T-cell receptor Vbeta gene segments in the CD8(+)-T-cell response to an immunodominant Moloney leukemia virus-encoded epitope in vivo.

Détails

ID Serval
serval:BIB_81142885E6C4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hierarchal utilization of different T-cell receptor Vbeta gene segments in the CD8(+)-T-cell response to an immunodominant Moloney leukemia virus-encoded epitope in vivo.
Périodique
Journal of virology
Auteur(s)
Brawand P., Cerottini J.C., MacDonald H.R.
ISSN
0022-538X
Statut éditorial
Publié
Date de publication
1999
Peer-reviewed
Oui
Volume
73
Numéro
11
Pages
9161-9169
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The CD8(+)-T-cell response to Moloney murine leukemia virus (M-MuLV)-associated antigens in C57BL/6 mice is directed against an immunodominant gag-encoded epitope (CCLCLTVFL) presented in the context of H-2D(b) and is restricted primarily to cytotoxic T lymphocytes (CTL) expressing the Valpha3.2 and Vbeta5.2 gene segments. We decided to examine the M-MuLV response in congenic C57BL/6 Vbeta(a) mice which are unable to express the dominant Valpha3.2(+) Vbeta5.2(+) T-cell receptor (TCR) due to a large deletion at the TCR locus that includes the Vbeta5.2 gene segment. Interestingly, M-MuLV-immune C57BL/6 Vbeta(a) mice were still able to reject M-MuLV-infected tumor cells and direct ex vivo analysis of peripheral blood lymphocytes from these immune mice revealed a dramatic increase in CD8(+) cells utilizing the same Valpha3.2 gene segment in association with two different Vbeta segments (Vbeta3 and Vbeta17). Surprisingly, all these CTL recognized the same immunodominant M-MuLV gag epitope. Analysis of the TCR repertoire of individual M-MuLV-immune (C57BL/6 x C57BL/6 Vbeta(a))F(1) mice revealed a clear hierarchy in Vbeta utilization, with a preferential usage of the Vbeta17 gene segment, whereas Vbeta3 and especially Vbeta5.2 were used to much lesser extents. Sequencing of TCRalpha- and -beta-chain junctional regions of CTL clones specific for the M-MuLV gag epitope revealed a diverse repertoire of TCRbeta chains in Vbeta(a) mice and a highly restricted TCRbeta-chain repertoire in Vbeta(b) mice, whereas TCRalpha-chain sequences were highly conserved in both cases. Collectively, our data indicate that the H-2D(b)-restricted M-MuLV gag epitope can be recognized in a hierarchal fashion by different Vbeta domains and that the degree of beta-chain diversity varies according to Vbeta utilization.
Mots-clé
Amino Acid Sequence, Animals, Cytophotometry, Cytotoxicity Tests, Immunologic, Cytotoxicity, Immunologic, Flow Cytometry, Gene Products, gag/immunology, Genes, T-Cell Receptor beta, Immunization, Immunodominant Epitopes/immunology, L-Selectin/metabolism, Mice, Molecular Sequence Data, Moloney murine leukemia virus/genetics, Moloney murine leukemia virus/immunology, Polymerase Chain Reaction/methods, Receptors, Antigen, T-Cell, alpha-beta/chemistry, Receptors, Antigen, T-Cell, alpha-beta/genetics, Sequence Analysis, DNA, T-Lymphocytes, Cytotoxic/immunology, Tumor Cells, Cultured
Pubmed
Web of science
Création de la notice
28/01/2008 12:13
Dernière modification de la notice
03/03/2018 18:47
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