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The human T cell response to myelin oligodendrocyte glycoprotein: a multiple sclerosis family-based study.

Abstract
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.
AuthorsNiklas K U Koehler, Claude P Genain, Barbara Giesser, Stephen L Hauser
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 168 Issue 11 Pg. 5920-7 (Jun 01 2002) ISSN: 0022-1767 [Print] United States
PMID12023398 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytokines
  • Epitopes, T-Lymphocyte
  • MOG protein, human
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
Topics
  • 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)

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