PERMISSIVE RECOGNITION OF IMMUNODOMINANT DETERMINANTS OF THE RETINAL S-ANTIGEN IN DIFFERENT RAT STRAINS, PRIMATES AND HUMANS

The majority of antigenic peptides exhibit restriction in their intera ction with the MHC molecules on antigen-presenting cells of different haplotypes, Certain peptides, however, are 'permissive': they bind str ongly to different MHC molecules and are selected as the immunodominan t epitopes by animals using these MHC gene products, Here we show for the first time that several peptides from four regions of the sequence of human S-antigen (H-SAS), a retinal-specific protein, demonstrate h igh levels of permissiveness, Each of these peptides was found to be i mmunodominant in at least some of four inbred rat strains and five cyn omolgus monkeys, immunized with whole H-SAg, Moreover, some of these p eptides were recognized by lymphocytes from four normal controls and f our patients with uveitis who responded against the H-SAg molecule. On the other hand, the permissive peptides stimulated marginal or no res ponse in cultures of Lewis rats injected with adjuvant alone, or rat a nd human cell lines specific to other antigens, thus demonstrating tha t these peptides do not carry any non-specific mitogenic activity, One peptide, 29, which was found immunodominant in the monkeys, the uveit is patients and Lewis rats, is highly immunopathogenic in this rat str ain, No good correlation between immunodominance and immunopathogenici ty was found with other H-SAg peptides, The finding of cross-species p ermissiveness among peptides of H-SAg and similar observations with my elin proteins suggest that permissiveness could be quite prevalent amo ng peptides of immunopathogenic antigens.