M. Allegretta et al., HOMOLOGIES BETWEEN T-CELL RECEPTOR JUNCTIONAL SEQUENCES UNIQUE TO MULTIPLE-SCLEROSIS AND T-CELLS MEDIATING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS, The Journal of clinical investigation, 94(1), 1994, pp. 105-109
The selection of T cell clones with mutations in the hypoxanthine guan
ine phosphoribosyltransferase (hprt) gene has been used to isolate T c
ells reactive to myelin basic protein (MBP) in patients with multiple
sclerosis (MS). These T cell clones are activated in vivo, and are not
found in healthy individuals. The third complementarity determining r
egions (CDR3) of the T cell receptor (TCR) alpha and beta chains are t
he putative contact sites for peptide fragments of MBP bound in the gr
oove of the HLA molecule. The TCR V gene usage and CDR3s of these MBP-
reactive hprt(-) T cell clones are homologous to TCRs from other T cel
ls relevant to MS, including T cells causing experimental allergic enc
ephalomyelitis (EAE) and T cells found in brain lesions and in the cer
ebrospinal fluid (CSF) of RIS patients. In vivo activated MBP-reactive
T cells in MS patients may be critical in the pathogenesis of MS.