CHARACTERIZATION OF THE SPECIFICITY AND DURATION OF T-CELL TOLERANCE TO INTRANASALLY ADMINISTERED PEPTIDES IN MICE - A ROLE FOR INTRAMOLECULAR EPITOPE SUPPRESSION

Mucosal administration of antigens in experimental animals leads to th e induction of peripheral T cell tolerance. We have previously reporte d that in H-2(b) mice, intranasal (i.n.) or oral administration of a p eptide containing the immunodominant T cell epitope will down-regulate the function of CD4(+) T cells reactive with Der p 1, a major target antigen in both a and T cell responses to house dust mite. In the pres ent study we have investigated the tolerogenicity of peptides containi ng both dominant and subdominant determinants when given i.n. to naive mice, Induction of tolerance by the nasally administered immunodomina nt peptide leads to a diminution in all T cell-derived cytokines and m odulation of delayed-type hypersensitivity responses, but IgE producti on did not seem to be affected, furthermore the induction of T cell to lerance was stable, lasting beyond 6 months, We have also examined the specificity of intramolecular epitope suppression which is a feature of mucosal tolerance induced by nasally administered peptides and demo nstrate that regulatory CD4(+) T cells may exert their suppressive eff ect by linked recognition of epitopes on the same or neighbouring anti gen-presenting cells.