The human T cell response to myelin oligodendrocyte glycoprotein: a multiple sclerosis family-based study.
Myelin oligodendrocyte glycoprotein (MOG) is an encephalitogenic myelin protein and a likely autoantigen in human multiple sclerosis (MS). In this work, we describe the fine specificity and cytokine profile of T cell clones (TCC) directed against MOG in three nuclear families, comprised of four individuals affected with MS and their HLA-identical siblings. TCC were generated from PBMC by limiting dilution against a mixture of eleven 20-mer overlapping peptides corresponding to the encephalitogenic extracellular domain of human MOG (aa 1-120). The frequency of MOG peptide-reactive T cells was surprisingly high (range, 1:400 to 1:3,000) and, unexpectedly, cloning efficiencies were highest at low seeding densities of 10(2) or 10(3) PBMC per well. A total of 235 MOG peptide-reactive TCC were produced, all of which were CD4(+)CD8(-)TCRalphabeta(+)TCRgammadelta(-). All 11 MOG peptides were recognized by the TCC, and different epitopes of MOG appeared to be immunodominant in the HLA-identical siblings. The patterns of cytokine secretion by TCC from single individuals were generally similar. The healthy individuals exhibited Th2-, Th0-, and T regulatory cell 1-like cytokine profiles, whereas TCC from one sibling with MS had a striking Th1-like phenotype, producing high levels of IFN-gamma and TNF-alpha, and low IL-4 levels. Thus, MOG-reactive T cells appear to constitute an important part of the natural T cell repertoire, a finding that could contribute to the development of autoimmunity to this protein.
Koehler
Niklas K U
NK
Department of Neurology, University of California, San Francisco, CA 94143, USA.
Genain
Claude P
CP
Giesser
Barbara
B
Hauser
Stephen L
SL
D000595:Amino Acid Sequence; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D016130:Immunophenotyping; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000209:etiology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein