REACTIVITY OF NORMAL T-CELL LINES TO MBP ISOLATED FROM NORMAL AND MULTIPLE-SCLEROSIS WHITE-MATTER

T-cell reactivity to human myelin basic protein (MBP) has been extensi vely studied using T-cell lines and clones generated from both periphe ral blood and cerebrospinal fluid, from normal controls and multiple s clerosis (MS) patients. These studies have largely utilized myelin bas ic protein isolated from control human adult white matter. In our stud y, we used MBP reactive T-cell lines as a probe to investigate antigen ic differences in a series of MBP preparations isolated from either co ntrol human white matter or white matter from the central nervous syst em (CNS) of MS patients. Autologous peripheral blood derived mononucle ar cells were used as antigen presenting cells (APC). Although the maj ority of T-cells were found to react equally well with all preparation s of MBP isolated from both control and MS white matter, we were also able to identify T-cell lines which reacted well with all preparations of MBP isolated from controls but failed to react with MBP isolated f rom MS white matter. These differences were unlikely to reflect differ ences in degradation products or excess peptides present in the MS bra in since SDS-PAGE and HPLC did not show any difference in the MS sampl es compared to the controls, and the concentration response curves for a human T-cell clone specific for the 84-102 region of MBP were simil ar for all the MBP preparations. We did not detect differences in amin o acid content amongst MBP preparations although single amino acid sub stitutions cannot be ruled out. These results raise the possibility th at MBP isolated from MS brain may differ in charge microheterogeneity which would affect antigenic determinants. The processing of MBP by di fferent APCs is another variable which could underlie the differences in T-cell reactivity to various MBP preparations.