[T cell immunity to proteolipid protein (PLP) in multiple sclerosis (MS): identification of DR2-associated PLP determinants and conserved TCR CDR3 motifs].
Multiple sclerosis is assumed to be an autoimmune disease mediated by T cells specific for myelin protein, such as, myelin basic protein (MBP) and PLP. Several groups reported that PLP-specific T cells are activated in the cerebrospinal fluid and, to a lesser extent, in the peripheral blood of the patients. We identified seven T cell epitopes within PLP residue 85-159. The T cell responses to these epitopes were higher in MS than in healthy subjects. PLP 95-116 and 105-124 specific T cells were more frequently established from DR2 MS than from non-DR2 MS, indicating that the DR2 restricted T cells recognizing these determinants are involved in the pathogenesis of MS. It is found PLP-specific T cells preferentially use V beta 5 and V beta 2 families though the usage is not exclusive. TCR beta chain complementary determining region 3 (CDR3) amino acid motifs of some PLP-specific T cells were homologous to those of MS lesion T cells, so it is likely that PLP-specific T cells infiltrate MS lesions. To our surprise, the CDR3 motifs of PLP-specific clones resemble those of MBP-specific clones. According to these facts, some antigen-independent pressure might give a common structure to T cells involved in MS.
Kondo
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Ohashi
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D000595:Amino Acid Sequence; D017124:Conserved Sequence; D000939:Epitopes / Q000032:analysis*; D015802:HLA-DR2 Antigen / Q000032:analysis*; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology*; D018991:Myelin Proteolipid Protein; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D015802:HLA-DR2 Antigen; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D011948:Receptors, Antigen, T-Cell