Selection of anti-myelin basic protein T-cell lines in the lewis rat: V-beta 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 Vbeta 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 Vbeta 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 Vbeta 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 Vbeta 8.2 and the characteristic CDR sequences are not seen. Thus, Vbeta 8.2 dominance and specific CDR3 TCR motifs are seen with heterologous GpMBP but not with self rat MBP.

A shared TCR CDR3 sequence in NOD mouse autoimmune diabetes.

T cells involved in autoimmune diseases have been characterized by the genetic elements used to construct their autoimmune TCR. In the present study, we sequenced the alpha and beta chains of the TCR expressed by a CD4(+) T cell clone, C9, functional in NOD mouse diabetes. Clone C9 can adoptively transfer diabetes or, when attenuated, C9 can be used to vaccinate NOD mice against diabetes. Clone C9 recognizes a peptide epitope (p277) of the 60 kDa heat shock protein (hsp60) molecule. We now report that the C9 TCR beta chain features a CDR3 peptide sequence that is prevalent among NOD mice. This CDR3 element is detectable by 2 weeks of age in the thymus, and later in the spleen and in the autoimmune insulitis. Thus, a TCR CDR3beta sequence appears to be a common idiotope associated with mouse diabetes.