T lymphocyte lines and clones selected against synthetic myelin basic protein 82-102 peptide from Japanese multiple sclerosis patients.
As has been indicated in experimental autoimmune encephalomyelitis (EAE), the application of synthetic peptides for the selection of T cell lines may provide new insights into the pathogenesis of multiple sclerosis (MS). We report here on T cell lines/clones generated from peripheral blood of MS patients against an immunodominant myelin basic protein (MBP) peptide 82-102. This study demonstrates that the selection of T cell lines against the MBP peptide is much more efficient than against whole MBP in generating a large panel of T cell lines/clones, and therefore provides a powerful strategy for studying autoimmune T cell repertoire in individual subjects. The peptide-selected lines and clones recognized MBP 82-102, shorter peptides MBP 89-101, 89-100 and guinea pig whole MBP mainly in the context of HLA-DR, but did not cross-recognize virus-derived peptides homologous to MBP 82-102. Seven out of ten clones were found to recognize MBP 82-102 in the absence of autologous antigen presenting cells (APC), and in three of the seven clones, specificity for MBP 82-102 could be demonstrated only in the absence of APC because of their strong reactivity against autologous APC. Two-color flow cytometry revealed that the clones were heterogeneous with regard to expression of CD4 and CD8 molecules. Overall, the clones selected by the peptide were rather heterogeneous in phenotype and function compared with those selected by whole MBP.
Inobe
J
J
Division of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Yamamura
T
T
Kunishita
T
T
Tabira
T
T
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003429:Cross Reactions; D004770:Enterovirus / Q000276:immunology; D005260:Female; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007564:Japan; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013552:Swine; D013555:Swine Vesicular Disease / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D006681:HLA-D Antigens; D004676:Myelin Basic Protein; D010455:Peptides