Article: article from journal or magazin.
The diversity of antigen-specific TCR repertoires reflects the relative complexity of epitopes recognized.
Publication types: Journal Article ; Review Publication Status: ppublish
Antigen-selected T cell receptor (TCR) repertoires vary in complexity from very limited to extremely diverse. We have previously characterized two different CD8 T cell responses, which are restricted by the same mouse major histocompatibility complex (MHC) class I molecule, H-2 Kd. The TCR repertoire in the response against a determinant from Plasmodium berghei circumsporozoite protein (PbCS; region 252-260) is very diverse, whereas TCRs expressed by clones specific for a determinant in region 170-179 of HLA-CW3 (human) MHC class I molecule show relatively limited structural diversity. We had already demonstrated that cytolytic T lymphocyte (CTL) clones specific for the PbCS peptide display diverse patterns of antigen recognition when tested with a series of single Ala-substituted PbCS peptides or mutant. H-2 Kd molecules. We now show that CW3-specific CTL clones display much less diverse patterns of recognition. Our earlier functional studies with synthetic peptide variants suggested that the optimal peptides recognized were 9 (or 8) residues long for PbCS and 10 residues long for CW3. We now present more direct evidence that the natural CW3 ligand is indeed a 10-mer. Our functional data together with molecular modeling suggest that the limited TCR repertoire selected during the CW3 response is not due to a paucity of available epitopes displayed at the surface of the CW3 peptide/Kd complex. We discuss other factors, such as the expression of similar self MHC peptide sequences, that might be involved in trimming this TCR repertoire.
Animals, Antigen Presentation, Cytotoxicity, Immunologic, Epitopes/genetics, Epitopes/immunology, H-2 Antigens/immunology, HLA Antigens/immunology, Histocompatibility Antigens Class I/immunology, Humans, Mice, Models, Immunological, Peptides/immunology, Receptors, Antigen, T-Cell/genetics, Receptors, Antigen, T-Cell/immunology, Recombinant Proteins/immunology, T-Lymphocyte Subsets/immunology
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