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| 001 | 296018 | ||
| 005 | 20250220163816.0 | ||
| 024 | 7 | _ | |a 10.1016/j.str.2024.11.014 |2 doi |
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| 100 | 1 | _ | |a Günther, Matthias |0 P:(DE-He78)63f0928851cb60021a60e05e4c196aae |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Antigen presentation by MHC-II is shaped by competitive and cooperative allosteric mechanisms of peptide exchange. |
| 260 | _ | _ | |a Cambridge, Mass. |c 2025 |b Cell Press |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1739195445_13025 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:B086#LA:B086# / 2025 Feb 6;33(2):389-400.e13 |
| 520 | _ | _ | |a Major histocompatibility complex class II (MHC-II) presents antigens to T helper cells. The spectrum of presented peptides is regulated by the exchange catalyst human leukocyte antigen DM (HLA-DM), which dissociates peptide-MHC-II complexes in the endosome. How susceptible a peptide is to HLA-DM is mechanistically not understood. Here, we present a data-driven mathematical model for the conformational landscape of MHC-II that explains the wide range of measured HLA-DM susceptibilities and predicts why some peptides are largely HLA-DM-resistant. We find that the conformational plasticity of MHC-II mediates both allosteric competition and cooperation between peptide and HLA-DM. Competition causes HLA-DM susceptibility to be proportional to the intrinsic peptide off-rate. Remarkably, diverse MHC-II allotypes with conserved HLA-DM interactions show a universal linear susceptibility function. However, HLA-DM-resistant peptides deviate from this susceptibility function; we predict resistance to be caused by fast peptide association with MHC-II. Thus, our study provides quantitative insight into peptide and MHC-II allotype parameters that shape class-II antigen presentation. |
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| 650 | _ | 7 | |a HLA-DM |2 Other |
| 650 | _ | 7 | |a HLA-DM susceptibility |2 Other |
| 650 | _ | 7 | |a MHC class-II |2 Other |
| 650 | _ | 7 | |a antigen presentation |2 Other |
| 650 | _ | 7 | |a immunopeptidome prediction |2 Other |
| 650 | _ | 7 | |a mathematical model |2 Other |
| 700 | 1 | _ | |a Sticht, Jana |b 1 |
| 700 | 1 | _ | |a Freund, Christian |b 2 |
| 700 | 1 | _ | |a Höfer, Thomas |0 P:(DE-He78)9dbe272aaadbdc810ab0bb291eae428e |b 3 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1016/j.str.2024.11.014 |g p. S0969212624005276 |0 PERI:(DE-600)2031189-8 |n 2 |p 389-400.e13 |t Structure |v 33 |y 2025 |x 0969-2126 |
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