Induction of Unresponsiveness in Adult Rats by Immunodominant and Nondominant Peptides

Intravenous (iv) administration of antigens in aqueous solution is an efficient procedure for inducing unresponsiveness in adult animals. Using this procedure, we have compared the unresponsiveness-inducing capacity or an immunodominant and a nondominant peptide derived from the sequence of a retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). The immunodominant peptide, R16, is highly immunogenic in the Lewis rat, while the nondominant peptide, R4, is much less immunogenic and requires higher doses to induce immune response. Pretreatment of Lewis rats with peptides R4 or R16 effectively induced unresponsiveness, shown by the reduced lymphocyte responses following the challenge with the same peptide in adjuvant emulsion. A correlation was found between the doses of each peptide needed to induce immunity or unresponsiveness: both of these doses had to be higher for peptide R4 than for R16. Remarkably, the minimal unresponsiveness-inducing doses of both peptides were lower than those used for the challenge. Pretreatment with the immunodominant peptide, R16, readily inhibited the response to this peptide by lymphocytes from rats challenged with whole IRBP and excessive doses of R16 even affected the response of these rats against whole IRBP. In contrast, R4, which is not recognized by cells of rats challenged with whole IRBP, had no effect on the responses of them rats. The data thus underscore the relationship between immunodominance and unresponsiveness-inducing capacity of peptides and support the notion that the processes of unresponsiveness induction are related to those that produce immunity.