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 interactionwith the MHC molecules on antigen-presenting cells of different haplotypes.Certain peptides, however, are "permissive': they bind strongly todifferent MHC molecules and are selected as the immunodominant epitopes byanimals using these MHC gene products. Here we show for the first time thatseveral peptides from four regions of the sequence of human S-antigen(H-SAg), a retinal-specific protein, demonstrate high levels ofpermissiveness. Each of these peptides was found to be immunodominant in atleast some of four inbred rat strains and five cynomolgus monkeys,immunized with whole H-SAg. Moreover, some of these peptides wererecognized by lymphocytes from four normal controls and four patients withuveitis who responded against the H-SAg molecule. On the other hand, thepermissive peptides stimulated marginal or no response in cultures of Lewisrats injected with adjuvant alone, or rat and human cell lines specific toother antigens, thus demonstrating that these peptides do not carry anynon-specific mitogenic activity. One peptide, 29, which was foundimmunodominant in the monkeys, the uveitis patients and Lewis rats, ishighly immunopathogenic in this rat strain. No good correlation betweenimmunodominance and immunopathogenicity was found with other H-SAgpeptides. The finding of cross-species permissiveness among peptides ofH-SAg and similar observations with myelin proteins suggest thatpermissiveness could be quite prevalent among peptides of immunopathogenicantigens.