DIVERSE T-CELL RECEPTOR BETA-CHAIN USAGE BY RAT ENCEPHALITOGENIC T-CELLS REACTIVE TO RESIDUES 68-88 OF MYELIN BASIC-PROTEIN

Encephalitogenic T cells not only cause experimental autoimmune encephalomyelitis (EAE), but they induce resistance against subsequent induction of the disease as well. The T cell receptor (TcR) of encephalitogenic T cells is believed to contribute to their vaccinating activity. Findings in support of this assumption include the apparent restricted use of particular TcR elements, such as Vbeta8.2. However, results from other laboratories including ours do not support this idea. We previously showed that rat T cells reactive against the conserved encephalitogenic epitope of myelin basic protein [MBP (87-99)] use the TcR in a heterogeneous fashion (Sun, D. et al., Eur. J. Immunol. 1992, 22: 591). Here we show, in Lewis rats, that the TcR beta chain usage of T cells specific for the dominant MBP (68-88) epitope is not restricted to Vbeta8.2. Not only did such cells rely on diverse Vbeta chains, but some non-Vbeta8-bearing cells were highly encephalitogenic. We also show that antigen-presenting cells (APC) play an important role in determining the TcR usage of MBP-specific T cells. Stimulation of MBP (68-88)-specific Tcell lines by cloned APC derived from different sources resulted in selection of encephalitogenic T cells bearing different TcR beta chains.