In:
The Journal of Immunology, The American Association of Immunologists, Vol. 168, No. 11 ( 2002-06-01), p. 5920-5927
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 102 or 103 PBMC per well. A total of 235 MOG peptide-reactive TCC were produced, all of which were CD4+CD8−TCRαβ+TCRγδ−. 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-γ and TNF-α, 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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.168.11.5920
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2002
detail.hit.zdb_id:
1475085-5
Bookmarklink