Enhanced T cell responsiveness to citrulline-containing myelin basic protein in multiple sclerosis patients

Myelin basic protein (MBP), a candidate autoantigen in multiple sclerosis ( MS), exists in different isoforms and charge isomers generated by different ial splicing of exons and by a combination of posttranslational modificatio ns respectively These various isoforms and charge isomers of MBP vary in ab undance and most likely serve different functions during myelinogenesis and remyelination. The least cationic among the charge isomers of MBP is citru llinated and is referred to as MBP-C8. MBP-C8 is relatively increased in th e population of MBP isomers in more developmentally immature myelin and in MS brain tissue. In a previous study, we found that MBP-C8-reactive T cells could be detected in CD4+ T cell lines (TCL) generated with MBP from both MS patients and normal controls. Here, we examined the frequency and peptid e specificity of MBP-C8-specific TCL generated with MBP-C8 in MS patients a nd controls. Ten subjects grouped in five sets, each on MS patient and a co ntrol, were studied. In all cases, the MS patient had either a higher overa ll number of MBP-C8-responding lines, responded with greeter sensitivity to the MBP-C8 antigen or both. Few lines responded to the MBP-C8 peptides but if they did, they appeared to be specific to the carboxyl-half of the MBP- C8 molecule. Given the large amounts of citrullinated MBP in MS brain tissu e, a preferential T cell response to MBP-C8 may be involved in the inductio n and perpetuation of this disease.