6xp6
3C11-DQ2-glia-a2 complex3C11-DQ2-glia-a2 complex
Structural highlights
Publication Abstract from PubMedAntibodies specific for peptides bound to human leukocyte antigen (HLA) molecules are valuable tools for studies of antigen presentation and may have therapeutic potential. Here, we generated human T cell receptor (TCR)-like antibodies toward the immunodominant signature gluten epitope DQ2.5-glia-alpha2 in celiac disease (CeD). Phage display selection combined with secondary targeted engineering was used to obtain highly specific antibodies with picomolar affinity. The crystal structure of a Fab fragment of the lead antibody 3.C11 in complex with HLA-DQ2.5:DQ2.5-glia-alpha2 revealed a binding geometry and interaction mode highly similar to prototypic TCRs specific for the same complex. Assessment of CeD biopsy material confirmed disease specificity and reinforced the notion that abundant plasma cells present antigen in the inflamed CeD gut. Furthermore, 3.C11 specifically inhibited activation and proliferation of gluten-specific CD4(+) T cells in vitro and in HLA-DQ2.5 humanized mice, suggesting a potential for targeted intervention without compromising systemic immunity. A high-affinity human TCR-like antibody detects celiac disease gluten peptide-MHC complexes and inhibits T cell activation.,Frick R, Hoydahl LS, Petersen J, du Pre MF, Kumari S, Berntsen G, Dewan AE, Jeliazkov JR, Gunnarsen KS, Frigstad T, Vik ES, Llerena C, Lundin KEA, Yaqub S, Jahnsen J, Gray JJ, Rossjohn J, Sollid LM, Sandlie I, Loset GA Sci Immunol. 2021 Aug 20;6(62):eabg4925. doi: 10.1126/sciimmunol.abg4925. PMID:34417258[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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