Immune Responses against Self-TCR Peptides

Vaccination of rats against the TCR peptide Vβ8.2 (39-59) was reported to inhibit the immunopathogenic process of EAE. Analysis of the immune response to this peptide and several related TCR peptides yielded the following findings: (i) Lewis rats immunized in vivo and challenged in vitro responded with vigorous lymphocyte proliferative responses to peptide Vβ8.2 (39-59) and to three other rat TCR peptides, Vβ8.3 (15-32), Vβ8.3 (39-59), and Vβ14 (39-59). On the other hand, two other rat peptides, Vβ8.2 (18-38) and Vβ8.3 (62-76), were poorly immunogenic. (ii) Rat peptide Vβ8.2 (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 between these two peptide homologs. (iii) Rats of different genetic makeups varied in their response to peptide Vβ8.2 (39-59). A similar pattern of response of the different rats was found with another TCR peptide, Vβ14 (39-59). Hybrids between high and low responder rat strains resembled the high responders in their response to the TCR peptides. (iv) Sensitized lymph node cells as web as lymphocytes of a cell line specific for peptide Vβ8.2 (39-59) failed to respond to T cells that express the Vβ8.2 gene product. This observation is interpreted to indicate that peptide Vβ8.2 (39-59) is a cryptic determinant of the Vβ8.2 protein. Moreover, the data suggest that lymphocytes proliferating against peptide Vβ8.2 (39-59) may not be responsible for the reported inhibition of EAE in rats vaccinated with this peptide.