title: Selection of antigen-specific T cells by a single IEk peptide combination.
abstract: In normal mice, major histocompatibility complex (MHC) proteins are bound to many different peptides, derived from the proteins of their host. In the thymus, the diversity of this collection of MHC + peptide ligands allows thymocytes bearing many different T cell receptors (TCRs) to mature by low avidity reactions between the MHC + peptide ligands and the thymocyte TCRs. To investigate this problem, the selection of T cells specific for a well-studied combination of MHC + peptide, IEk + moth cytochrome c 88-103 (MCC), was investigated. Mice were created that expressed IEk bound to a single peptide, either a variant of MCC in which a critical TCR contact residue, 99K, was changed to A, or a variant of a mouse hemoglobin 64-76 (Hb) peptide, 72A. IEk bound to the MCC variant caused the clonal deletion of some T cells specific for the IEk + MCC ligand; nevertheless, it also positively selected many T cells that could react with this ligand. Some of the TCRs on the selected T cells were related to those on cells from normal mice and some were not. IEk bound to the Hb variant, on the other hand, did not select any T cells which could react with IEk + MCC. These results demonstrate that although positive selection is a partially degenerate event, the sequence of the peptide involved in positive selection controls the selected repertoire.
authors.affiliation: Howard Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Parker
authors.forename: J
authors.initials: J
authors.lastname: Kappler
authors.forename: P
authors.initials: P
authors.lastname: Marrack
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017637:Clonal Deletion / Q000235:genetics; D003574:Cytochrome c Group / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009036:Moths; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000276:immunology
chemical_list: D003574:Cytochrome c Group; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell