Diversity of T cell receptor alpha 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.
Department of Neuroimmunology, Max-Planck Institute for Psychiatry, Martinsried.
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Giegerich
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Pette
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Meinl
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JT
Epplen
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Wekerle
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Hinkkanen
D000595:Amino Acid Sequence; D015551:Autoimmunity; D001483:Base Sequence; D002999:Clone Cells; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta