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-Structure paper
| タイトル | A general system for targeting MHC class II-antigen complex via a single adaptable loop. |
|---|---|
| ジャーナル・号・ページ | Nat Biotechnol, Vol. 43, Issue 10, Page 1673-1682, Year 2025 |
| 掲載日 | 2024年12月13日 |
著者 | Haotian Du / Jingjia Liu / Kevin M Jude / Xinbo Yang / Ying Li / Braxton Bell / Hongli Yang / Audrey Kassardjian / Wyatt Blackson / Ali Mobedi / Udit Parekh / R Andres Parra Sperberg / Jean-Philippe Julien / Elizabeth D Mellins / K Christopher Garcia / Po-Ssu Huang / ![]() |
| PubMed 要旨 | Major histocompatibility complex class II (MHCII) bound to a peptide antigen mediates interactions between CD4 T cells and antigen-presenting cells. Targeting peptide-MHCII with T cell antigen ...Major histocompatibility complex class II (MHCII) bound to a peptide antigen mediates interactions between CD4 T cells and antigen-presenting cells. Targeting peptide-MHCII with T cell antigen receptors (TCRs) and TCR-like antibodies has shown promise for autoimmune diseases and microbiome tolerance. To develop a general targeting approach, we introduce targeted recognition of antigen-MHC complex reporter for MHCII (TRACeR-II) for the rapid development of peptide-specific MHCII binders. TRACeR-II binders have a small helical bundle scaffold and use a single loop to recognize peptide-MHCII, which offers versatility and enables structural modeling of the interactions to target MHCII antigens. We demonstrate rapid generation of TRACeR-II binders to multiple molecules with affinities in the low-nanomolar to low-micromolar range, comparable to best-in-class TCRs and antibodies. Through computational protein design, we created specific binding sequences in silico from only the sequence of a severe acute respiratory syndrome coronavirus 2 peptide. TRACeR-II provides a straightforward approach to target antigen-MHCII without relying on combinatorial selection on complementarity-determining region loops. |
リンク | Nat Biotechnol / PubMed:39672953 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.28 Å |
| 構造データ | EMDB-43499, PDB-8vsj: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | IMMUNE SYSTEM / complex / engineered protein |
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homo sapiens (ヒト)
metamycoplasma arthritidis (バクテリア)
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