8tbp

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Current revision (09:57, 17 October 2024) (edit) (undo)
 
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8tbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tbp OCA], [https://pdbe.org/8tbp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tbp RCSB], [https://www.ebi.ac.uk/pdbsum/8tbp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tbp ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8tbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tbp OCA], [https://pdbe.org/8tbp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tbp RCSB], [https://www.ebi.ac.uk/pdbsum/8tbp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tbp ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
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== Publication Abstract from PubMed ==
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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.
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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<ref>PMID:38321013</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 8tbp" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
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</StructureSection>
</StructureSection>

Current revision

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

PDB ID 8tbp

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