Selection of anti-myelin basic protein T-cell lines in the Lewis rat: V- β 8.2 dominance and conserved complementarity-determining-region-3 motifs are dependent on serine at position 78 of myelin basic protein

In the Lewis rat, the dominant T cell repertoire to myelin basic protein (MBP) is directed to the peptide 71-87 and the T cell receptors of pathogenic T cells are of the Vβ 8.2 genotype with short CDR3 sequences having a characteristic motif. However, this paradigm has been reached through analysis of long-term encephalitogenic lines and clones. We initiated the present study to examine the process of selection of the TCR Vβ 8.2 and characteristic CDR3 motifs upon immunization with guinea-pig MBP, and rat or guinea-pig 71-87 peptides. We found that the dominance of Vβ 8.2 developed progressively over 4-6 in vitro stimulations. Following immunization with rat 70-86, which differs from the guinea-pig peptide in one amino acid at position 78, the dominance of Vβ 8.2 and the characteristic CDR sequences are not seen. Thus, Vβ 8.2 dominance and specific CDR3 TCR motifs are seen with heterologous GpMBP but not with self rat MBP. (C) 2000 Elsevier Science B.V.