IMMUNE-RESPONSES AGAINST SELF-TCR PEPTIDES

Vaccination of rats against the TCR peptide V beta 8.2 (39-59) was rep orted to inhibit the immunopathogenic process of EAE. Analysis of the immune response to this peptide and several related TCR peptides yield ed the following findings: (i) Lewis rats immunized in vivo and challe nged in vitro responded with vigorous lymphocyte proliferative respons es to peptide V beta 8.2 (39-59) and to three other rat TCR peptides, V beta 8.3 (15-32), V beta 8.3 (39-59), and V beta 14 (39-59). On the other hand, two other rat peptides, V beta 8.2 (18-38) and V beta 8.3 (62-76), were poorly immunogenic. (ii) Rat peptide V beta 8.2 (39-59) was found more immunogenic than its mouse homolog, in both Lewis rats and B10.A mice. A moderate level of cross-reactivity was observed betw een these two peptide homologs. (iii) Rats of different genetic makeup s varied in their response to peptide V beta 8.2 (39-59), A similar pa ttern of response of the different rats was found with another TCR pep tide, V beta 14 (39-59), Hybrids between high and low responder rat st rains resembled the high responders in their response to the TCR pepti des. (iv) Sensitized lymph node cells as well as lymphocytes of a cen line specific for peptide V beta 8.2 (39-59) failed to respond to T ce lls that express the V beta 8.2 gene product. This observation is inte rpreted to indicate that peptide V beta 8.2 (39-59) is a cryptic deter minant of the V beta 8.2 protein. Moreover, the data suggest that lymp hocytes proliferating against peptide V beta 8.2 (39-59) may not be re sponsible for the reported inhibition of EAE in rats vaccinated with t his peptide. (C) 1994 Academic Press, Inc.