A major influence of the T cell receptor repertoire as compared to antigenprocessing-presentation in the selection of myelin basic protein epitopes in multiple sclerosis

We selected two multiple sclerosis (MS) patients, compatible for HLA-DR2 su btype, and differing for HLA-DM haplotype as well as for the myelin basic p rotein (MBP) epitope recognized by the vast majority of their T cell lines (TCL) (residues 16-38 and 86-99, respectively). TCL sharing the same restri ction element were re-assayed in the presence of reciprocally mismatched an tigen-presenting cells (APC). The TCL recognized both the whole MBP and the relevant peptide also in the presence of non-autologous APC, (compatibilit y for processing, despite a difference in the DM haplotype). The same proto col. performed in serum-free pulsing experiments or in the presence of 'fix ed' APC, excluded extracellular processing or mutual T cell presentation, a nd confirmed the need for MBP processing in our system. The finding, that o nly TCL recognizing MBP peptide 16-38 (a region not previously related to t he DR2 haplotype) used a novel VP, supports the importance of the TCR reper toire over the processing-presentation machinery in the selection of MBP ep itopes in MS. (C) 1999 Elsevier Science B.V. All rights reserved.