IDENTIFICATION OF A 2ND T-CELL EPITOPE OF HUMAN PROTEOLIPID PROTEIN (RESIDUES 89-106) RECOGNIZED BY PROLIFERATIVE AND CYTOLYTIC CD4-CELLS FROM MULTIPLE-SCLEROSIS PATIENTS( T)

Research into the pathogenesis of multiple sclerosis (MS) has focused on myelin antigens as potential targets of autoimmune attack. Proteoli pid protein (PLP) is the most abundant myelin protein comprising more than 50% of central nervous system myelin. Although PLP is a hydrophob ic membrane protein which has made it difficult to study, the use of s ynthetic peptides based on the PLP sequence provides an alternative me thod for studying the immunological properties of PLP. Using periphera l blood lymphocytes from MS patients, long-term TCL established in the presence of PLP reacted weakly to PLP in proliferation assays; howeve r, these same lines were much more reactive to synthetic peptides of P LP. Thus, we established short-term T cell lines (TCL) from the periph eral blood lymphocytes (PBL) of MS patients in the presence of five se parate synthetic PLP peptides. In 6/7 MS patients, proliferative respo nses were elicited most often to PLP 40-60 compared to four other PLP peptides (PLP 89-106, 103-120, 125-143, and 139-154) (Pelfrey et al., 1993). Interestingly, however, the magnitude of the proliferative resp onse was greatest in response to PLP 89-106. Characterization of PLP 8 9-106-responsive TCL from several MS patients, indicated that TCL prol iferating to the peptide also lysed PLP 89-106 pulsed autologous targe ts. The majority of cytolytic PLP 89-106 TCL were CD4(+) and MHC class II restricted and the predominant restriction elements were those mos t commonly found in MS patients. These findings suggest that the use o f synthetic peptides represents a viable alternative approach to the s tudy of PLP reactivity in humans. We report here that MS PBL recognize several PLP peptides, with the predominant responses to PLP 40-60 and PLP 89-106. Since these cells have both helper (CD4(+)) and cytolytic capabilities, it is possible that they may play a role in the pathoge nesis or progression of MS.