POSSIBLE MECHANISM FOR THE TCR-BETA-CHAIN ASSOCIATED EAE RESISTANCE OF LER RATS

LER rats are resistant to the active induction of experimental allergi c encephalomyelitis (EAE), The mechanism of their resistance to EAE ha s yet to be defined, although LER rats are susceptible to adoptively t ransferred EAE, Genetic analysis of LER and the susceptible LEW rat su ggests that a gene linked to the T cell receptor (TCR) beta-chain comp lex contributes to EAE resistance, This result is consistent with the fact that EAE is a T cell mediated disease and one characterized in EA E-susceptible animals by an oligoclonal TCR V beta 8.2+ response. In t his report, analysis of TCR transcripts by reverse transcriptase polym erase chain reaction (RT-PCR) and restriction digestion demonstrates t hat LER lymph nodes, collected on day 10 post-immunization with myelin basic protein (MBP), express both TCR-V beta 8.2 and other TCR beta c hains, usually V beta 8.4, whereas LEW animals demonstrate preferentia l and almost exclusive use of V beta 8.2 TCR. Fluorescence-activated c ell sorting (FAGS) analyses of anti-MBP T cells confirm that LER T cel ls express V beta 8.2 TCR to a lesser degree than LEW T cells. Finally , experiments examining the oligo- or polyclonality of the TCRV beta C DR3 region show that the LER response to MBP is polyclonal, while the LEW response to MBP is oligoclonal, Therefore, the cumulative data on the TCR usage profiles in this report suggest that the choice of TCR v ariable beta-chain may contribute to the resistance seen in the LER ra t. (C) 1996 Wiley-Liss, Inc.