title: The diversity of antigen-specific TCR repertoires reflects the relative complexity of epitopes recognized.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
authors.forename: J L
authors.initials: JL
authors.lastname: Maryanski
authors.forename: J L
authors.initials: JL
authors.lastname: Casanova
authors.forename: K
authors.initials: K
authors.lastname: Falk
authors.forename: H
authors.initials: H
authors.lastname: Gournier
authors.forename: C
authors.initials: C
authors.lastname: Jaulin
authors.forename: P
authors.initials: P
authors.lastname: Kourilsky
authors.forename: F A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: R
authors.initials: R
authors.lastname: Lüthy
authors.forename: H G
authors.initials: HG
authors.lastname: Rammensee
authors.forename: O
authors.initials: O
authors.lastname: Rötzschke
authors.forename: C
authors.initials: C
authors.lastname: Servis
authors.forename: J A
authors.initials: JA
authors.lastname: López
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000939:Epitopes; D006183:H-2 Antigens; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins