H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity

Details

Serval ID
serval:BIB_4DFF180AD748
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity
Journal
Journal of Experimental Medicine
Author(s)
Casanova  J. L., Cerottini  J. C., Matthes  M., Necker  A., Gournier  H., Barra  C., Widmann  C., MacDonald  H. R., Lemonnier  F., Malissen  B., Maryanski  J.L
ISSN
0022-1007 (Print)
Publication state
Published
Issued date
08/1992
Volume
176
Number
2
Pages
439-47
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Aug 1
Abstract
We previously showed that H-2Kd-restricted cytotoxic T lymphocyte (CTL) clones specific for a single nonapeptide derived from the Plasmodium berghei circumsporozoite (PbCS) protein displayed T cell receptors (TCRs) of highly diverse primary structure. We have now analyzed the TCR repertoire of CTLs that recognize a peptide derived from the human class I major histocompatibility complex (MHC) molecule HLA-Cw3 in association with the same murine class I MHC molecule H-2Kd. We first sequenced the TCR alpha and beta genes of the CTL clone Cw3/1.1 and, based on this genomic analysis, the TCR alpha and beta cDNA junctional regions of 23 independent H-2Kd-restricted CTL clones specific for HLA-Cw3. The results show that the TCR chains display very limited heterogeneity, both in terms of V alpha, J alpha, V beta, and J beta segments, and in terms of length and sequence of the CDR3 alpha and beta loops. The TCR repertoire used in vivo was then analyzed by harvesting CTL populations from the peritoneal cavity of immune mice. The peritoneal exudate lymphocytes (PELs) displayed HLA-Cw3-specific cytolytic activity in the absence of any stimulation in vitro. Remarkably, most of these freshly isolated PELs expressed TCRs that shared the same structural features as those from HLA-Cw3-reactive CTL clones. Thus, our results show that a peptide from HLA-Cw3 presented by H-2Kd selects CTLs that bear TCRs of very limited diversity in vivo. When taken together with the high diversity of the TCRs specific for the PbCS peptide, these findings suggest that natural tolerance to self peptides presented by class I MHC molecules may substantially reduce the size of the TCR repertoire of CTLs specific for antigenic peptides homologous to self.
Keywords
Amino Acid Sequence Animals Base Sequence Chromatography, Thin Layer Dna Epitopes Gene Rearrangement, beta-Chain T-Cell Antigen Receptor H-2 Antigens/*immunology HLA-C Antigens/genetics/*immunology Immune Tolerance Mice Mice, Inbred DBA Molecular Sequence Data Peptide Fragments/chemical synthesis/immunology Receptors, Antigen, T-Cell/genetics/*immunology Restriction Mapping T-Lymphocytes, Cytotoxic/*immunology Transfection
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:14
Last modification date
20/08/2019 14:03
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