8TBP

HLA-DRB1*15:01 in complex with smith antigen

Summary for 8TBP

• Entry DOI: 10.2210/pdb8tbp/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1 beta chain, Small nuclear ribonucleoprotein-associated protein N peptide, ... (5 entities in total)
• Functional Keywords: human leukocyte antigen, hla, major histocompatibility complex, mhc, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 90241.45

Authors

Ting, Y.T.,Broury, A.,Ooi, J. (deposition date: 2023-06-29, release date: 2024-02-21, Last modification date: 2024-10-16)

Primary citation

Eggenhuizen, P.J.,Cheong, R.M.Y.,Lo, C.,Chang, J.,Ng, B.H.,Ting, Y.T.,Monk, J.A.,Loh, K.L.,Broury, A.,Tay, E.S.V.,Shen, C.,Zhong, Y.,Lim, S.,Chung, J.X.,Kandane-Rathnayake, R.,Koelmeyer, R.,Hoi, A.,Chaudhry, A.,Manzanillo, P.,Snelgrove, S.L.,Morand, E.F.,Ooi, J.D.
Smith-specific regulatory T cells halt the progression of lupus nephritis.
Nat Commun, 15:899-899, 2024

PubMed Abstract: Antigen-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.

PubMed: 38321013
DOI: 10.1038/s41467-024-45056-x

Experimental method

X-RAY DIFFRACTION (3.1262111426 Å)