In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 10 ( 2015-03-10), p. 3044-3049
Abstract:
Antigen-specific CD4 + T cells are implicated in the autoimmune disease systemic lupus erythematosus (SLE), but little is known about the peptide antigens that they recognize and their precise function in disease. We generated a series of MHC class II tetramers of I-E k –containing peptides from the spliceosomal protein U1-70 that specifically stain distinct CD4 + T-cell populations in MRL/ lpr mice. The T-cell populations recognize an epitope differing only by the presence or absence of a single phosphate residue at position serine 140 . The frequency of CD4 + T cells specific for U1-70(131-150):I-E k (without phosphorylation) correlates with disease severity and anti–U1-70 autoantibody production. These T cells also express RORγt and produce IL-17A. Furthermore, the U1-70–specific CD4 + T cells that produce IL-17A are detected in a subset of patients with SLE and are significantly increased in patients with mixed connective tissue disease. These studies provide tools for studying antigen-specific CD4 + T cells in lupus, and demonstrate an antigen-specific source of IL-17A in autoimmune disease.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1424796112
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2015
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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