8tbp
HLA-DRB1*15:01 in complex with smith antigen
Structural highlights
Publication Abstract from PubMedAntigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduce our lead Sm-specific TCR into Tregs derived from patients with SLE who are anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppress Sm-specific pro-inflammatory responses in vitro and suppress disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE. Smith-specific regulatory T cells halt the progression of lupus nephritis.,Eggenhuizen PJ, Cheong RMY, Lo C, Chang J, Ng BH, Ting YT, Monk JA, Loh KL, Broury A, Tay ESV, Shen C, Zhong Y, Lim S, Chung JX, Kandane-Rathnayake R, Koelmeyer R, Hoi A, Chaudhry A, Manzanillo P, Snelgrove SL, Morand EF, Ooi JD Nat Commun. 2024 Feb 6;15(1):899. doi: 10.1038/s41467-024-45056-x. PMID:38321013[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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