DIVERSITY OF T-CELL RECEPTOR ALPHA-CHAIN AND BETA-CHAIN GENES EXPRESSED BY HUMAN T-CELLS SPECIFIC FOR SIMILAR MYELIN BASIC-PROTEIN PEPTIDE MAJOR HISTOCOMPATIBILITY COMPLEXES

T cell receptor (TcR) alpha and beta-nucleotide sequences involved in the human autoreactivity to myelin basic protein (MBP) were studied by screening cDNA libraries derived from 11 independent T lymphocyte clones (TCC) established from multiple sclerosis patients and healthy donors. The TCC with defined MBP peptide specificity and HLA-DR restriction expressed multiple TcR. Even TCC recognizing the same human MBP peptide [amino acids (aa) 139-153] in identical or very similar HLA-DR context expressed diverse TcR. Two TCC which recognized peptide aa 139-153 equally well in the context of both HLA-DR2a and -DR1 molecules used distinct TcR-alpha but identical beta-chains. The knowledge of TcR-beta and TcR-alpha-chain sequences of human MBP-specific T cells will allow studies correlating structure and function of TcR and their targets in MBP autoreactivity. This may have an impact on the development of immunotherapies in multiple sclerosis.