The Human T Cell Response to Myelin Oligodendrocyte Glycoprotein: A Multiple Sclerosis Family-Based Study

• Published in: The Journal of immunology (1950) Vol. 168; no. 11; pp. 5920 - 5927
• Main Authors: Koehler, Niklas K. U, Genain, Claude P, Giesser, Barbara, Hauser, Stephen L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.06.2002
• Subjects: Amino Acid Sequence; Cytokines - biosynthesis; Epitopes, T-Lymphocyte; Humans; Immunophenotyping; Molecular Sequence Data; Multiple Sclerosis - etiology; Myelin Proteins; Myelin-Associated Glycoprotein - immunology; Myelin-Oligodendrocyte Glycoprotein; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.11.5920

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.