Diversity of T-cell receptor V alpha, V beta, and CDR3 expression by myelin basic protein-specific human T-cell clones.

We sequenced the cDNAs of alpha and beta T-cell receptors (TCRs), including V, J, and CDR3 regions, expressed by 54 myelin basic protein (MBP)-specific T-cell clones generated from the peripheral blood of 15 multiple sclerosis (MS) patients and three normal controls. Thirteen V alpha gene segments, 18 V beta gene segments, 23 CDR3 alpha sequences, and 30 CDR3 beta sequences were represented among these clones. Some CDR3 motifs were common to several clones that shared epitope specificity, while other motifs were common to clones with diverse epitope specificities. The extensive heterogeneity of TCR gene expression in the human immune response to MBP indicates that therapeutic strategies aimed at blocking a limited number of TCRs are unlikely to fully suppress the T-cell response to MBP in vivo.