TREATMENT OF RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS WITHT-CELL RECEPTOR PEPTIDES

Restricted T cell receptor (TCR) VB gene usage by T cells for recognit ion of antigens involved in the production of experimental autoimmune encephalomyelitis (EAE) offers the possibility of selective immunother apy. We determined the preferential VB gene usage of lymph node-derive d clones from SJL/J mice to recognize the encephalitogenic epitope PLP 139-151 and from PL/J mice to recognize the newly described encephali togenic epitope PLP 43-64. In addition, the VB gene usage for recognit ion of PLP 139-151 by T cell lines derived from SJL/J spinal cords was analyzed. Lymph node-derived SJL/J lines and clones specific for PLP 139-151 expressed VB2, VB4, and VB17a preferentially, and PL/J lines a nd clones specific for PLP 43-64 expressed VB2 and VB8.2 preferentiall y. A VB4 + SJL/J clone and a VB8.2 + PL/J clone were encephalitogenic. Encephalitogenic SJL/J lines derived from spinal cord expressed VB2, VB10, VB16, and VB17a preferentially, with a predominance of VB2. Cand idate TCR peptides were synthesized and tested from the VB gene famili es VB4, VB8.2, and VB17a, based on our data and previous data on BP-in duced EAE in mice. Treatment of relapsing EAE (R-EAE) in SJL/J mice wi th VB4 and VB17a peptides reduced clinical and histological disease se verity, and treatment of R-EAE in (PLxSJL)F1 mice with VB4 and VB8.2 p eptides also reduced clinical and histological disease. The use of TCR peptide therapy may have applications for the treatment of human auto immune diseases such as multiple sclerosis.