The responses of mature T cells are not necessarily antagonized by their positively selecting peptide.

Transgenic mice have been produced in which all detectable MHC class II proteins, IAb, are bound to a single peptide. Hence, all of the CD4+ class II-restricted T cells in these animals are positively selected in the thymus by reaction with this single class II/peptide combination. It has been suggested that the peptide involved in positive selection of a particular T cell might antagonize the responses of that T cell to other peptides, a phenomenon that might serve to inhibit autoimmune reactions. To test this idea, we took advantage of the fact that T cells from the class II single-peptide mice react strongly in primary mixed lymphocyte cultures with IAb molecules from wild-type H-2b mice, i.e., loaded with a heterogeneous collection of self peptides. The responses of the T cells to other class II-bound peptides were not inhibited by high concentrations of the selecting peptide. Therefore, peptides involved in positive selection of T cells do not necessarily inhibit or antagonize the responses of mature T cells to Ag.