Epitope specificity and TCR V beta gene utilization in the encephalitogenic response of B10.RIII(71NS)/SnJ mice.

A high proportion of peptide 1-11 specific T cells from H-2u (V beta 8+, H-2u) mice express the V beta 8 TCR chain. Peptide 89-101 is immunodominant for B10.RIII (V beta 8+, H-2r) mice; thus, it was of interest to determine whether V beta 8 TCR would be over-represented in a population of peptide 89-101-specific T cells of this strain. Second, it was asked whether MBP peptides other than 89-101 would induce EAE in these mice. Of 70 B10.RIII(71NS)/SnJ mice immunized with mouse myelin basic protein (MBP), 32 of 41 males (78%) and 11 of 29 females (38%) showed clinical signs of experimental allergic encephalomyelitis (EAE). All mice immunized with peptide 89-101 showed clinical signs. One of six mice immunized with peptide 91-103 showed clinical signs, and 9 of 16 mice, all males, responded with EAE when immunized with peptide 38-88. No clinical EAE was observed in mice immunized with peptide 43-67, 68-88, 55-74, 1-37 or 1-20. A peptide 89-101-specific T cell line was established. At the initial stimulation the line was 29% V beta 8+ versus 21% in normal controls, and the line did not transfer EAE adoptively. After five in vitro stimulations, the percentage of V beta 8+ T cells had increased to 54%, and the line was encephalitogenic. Encephalitogenicity was partially blocked by anti-V beta 8 monoclonal antibody. Thus, over-representation of V beta 8+ TCR by encephalitogenic peptide-specific T cells is not limited to peptide 1-11-specific T cells from H-2u mice.(ABSTRACT TRUNCATED AT 250 WORDS)