A TCR Vα CDR3-specific motif associated with lewis rat autoimmune encephalomyelitis and basic protein-specific T cell clones

To investigate TCR Vα gene expression in the Lewis rat model of experimental autoimmune encephalomyelitis, we obtained Vα chain sequences from two Vβ8.2-encephalitogenic, BP72-89-specific T cell clones. Two different Vα genes, a Vα2 gene and a Vα23 gene, are utilized, but both were found to contain an asparagine repeat (Asn₃₊) sequence present in the Vα CDR3 region. This Asn₃₊ motif is also present in the previously reported sequence of a BP68-88-specific hybridoma, 510, which utilizes a different Vα2 gene family member. In further experiments, spinal cord T cells were isolated at the onset of basic protein (BP)-induced disease and sorted for the OX-40 activation marker, which we have previously used to enrich for specifically activated T cells. Analysis of Vα expression in the OX-40⁺ population revealed the biased use of three Vα genes, Vα1, Vα2, and Vα23. The Asn₃₊ motif was present in the Vα CDR3 region of Vα1, Vα2, and Vα23 cDNA derived from OX-40⁺ spinal cord T cells but found to be generally absent in the OX-40^- spinal cord population. Since these Asn₃₊ motif-bearing Vα chain sequences are nearly identical to those utilized by the BP-specific encephalitogenic clones described, it is likely that these Vα sequences are derived from disease-associated T cells in the spinal cord. Thus, we demonstrate that the Asn₃₊ Vα CDR3 motif is strongly associated with experimental autoimmune encephalomyelitis in the Lewis rat and propose that it plays a role in TCR recognition of a specific BP peptide/MHC complex.