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Tetramers reveal IL-17–secreting CD4 + T cells that are specific for U1-70 in lupus and mixed connective tissue disease

2015; National Academy of Sciences; Volume: 112; Issue: 10 Linguagem: Inglês

10.1073/pnas.1424796112

1091-6490

Nicole H. Kattah, Evan W. Newell, Justin A. Jarrell, Alvina D. Chu, Jianming Xie, Michael G. Kattah, Ofir Goldberger, Jessica Ye, Eliza F. Chakravarty, Mark M. Davis, Paul J. Utz,

Immune Cell Function and Interaction

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.