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 oft cells specific for a well- studied combination of MHC + peptide, IE(k) + moth cytochrome c 88-103 (MCC), was investigated. Mice were created that expressed IE(k) 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. IE(k) bound to the MCC variant caused the clonal deletion of some T cells specific for the IE(k) + 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. IE(k) bound to the Hb variant, on the other hand, did not select any T cells which could react with IE(k) + 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.
ASJC Scopus subject areas
- Immunology and Allergy