J Immunol 2002 Jun 1;168(11):5920-7
Koehler NK, Genain CP, Giesser B, Hauser SL.
Department of Neurology, University of California, San Francisco, CA 94143. Department of Neurology, University of Arizona, Tucson, AZ 85724.
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.