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.
Ignatowicz
L
L
Howard Hughes Medical Institute, Department of Medicine, National Jewish Center for Immunology, Denver, CO 80206, USA.
Kappler
J
J
Parker
D C
DC
Marrack
P
P
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D010455:Peptides