Involvement of distinct murine T-cell receptors in the autoimmune encephalitogenic response to nested epitopes of myelin basic protein

The peptide p89-101 (Val-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro) of myelin basic protein is encephalitogenic in mice expressing H-2(q) and H-2(s) antigens. Six of 13 encephalitogen-specific T-cell clones were shown to express the variable β-chain (V(β)) 17a gene product (KJ23a⁺), whereas seven clones were KJ23a^-. Both KJ23a⁺ and KJ23a^- subpopulations were encephalitogenic in SJL/J mice when adoptively transferred. Depletion of KJ23a⁺ cells in vivo with the administration of the antibody KJ23a suppresses experimental allergic encephalomyelitis induced with KJ23a⁺ T-cell lines. However, experimental allergic encephalomyelitis induced with either (i) encephalitogenic peptide p89-101, (ii) intact myelin protein, or (iii) KJ23a^- T cells reactive to p89-101 cannot be prevented with monoclonal antibody KJ23a. These data indicate that in spite of the V(β) 17a gene expression in a relatively large proportion of p89-101-specific T cells, such V(β) gene use is not essential for the induction of experimental allergic encephalomyelitis in SJL/J mice. These results contrast with the predominance of V(β) gene use (Vβ 8.2) in T cells reactive to the encephalitogenic fragment (pR1-11) in PL/J mice. One reason for this lack of dominant use of a particular T-cell receptor V(β) gene family in the autoimmune response to myelin basic protein in SJL/J mice stems from the observation that two encephalitogenic epitopes exist in p89-101. KJ23a^- T cells are stimulated by the deleted peptide p89-101, whereas KJ23a⁺ T cells are not. Thus, in the response to an encephalitogenic fragment of myelin basic protein containing two nested epitopes, at least two distinct T-cell receptor V(β) genes are expressed. These distinct T-cell subpopulations can each trigger experimental allergic encephalomyelitis. These findings have implications for therapy of autoimmune disease with antibodies to the T-cell receptor gene products.