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 interaction with the MHC molecules on antigen-presenting cells of different haplotypes. Certain peptides, however, are "permissive': they bind strongly to different MHC molecules and are selected as the immunodominant 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-SAg), a retinal-specific protein, demonstrate high levels of permissiveness. Each of these peptides was found to be immunodominant in at least some of four inbred rat strains and five cynomolgus monkeys, immunized with whole H-SAg. Moreover, some of these peptides were recognized by lymphocytes from four normal controls and four patients with uveitis who responded against the H-SAg molecule. On the other hand, the permissive peptides stimulated marginal or no response in cultures of Lewis rats injected with adjuvant alone, or rat and human cell lines specific to other antigens, thus demonstrating that these peptides do not carry any non-specific mitogenic activity. One peptide, 29, which was found immunodominant in the monkeys, the uveitis patients and Lewis rats, is highly immunopathogenic in this rat strain. No good correlation between immunodominance and immunopathogenicity was found with other H-SAg peptides. The finding of cross-species permissiveness among peptides of H-SAg and similar observations with myelin proteins suggest that permissiveness could be quite prevalent among peptides of immunopathogenic antigens.