Structural insights into human MHC- II association with invariant chain

• 成果类型: Article
• 署名作者: Wang, Nan; Waghray, Deepa; Caveney, Nathanael A.; Jude, Kevin M.; Garcia, K. Christopher
• 署名单位: Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10687
• DOI: 10.1073/pnas.2403031121
• 发表日期: 2024-05-07
• 关键词: hla-dm; transmembrane domain; crystal-structure; peptide; complex; trimerization; glycoproteins; prediction; subunit; PATHWAY

摘要

The loading of processed peptides on to major histocompatibility complex II (MHC - II) molecules for recognition by T cells is vital to cell - mediated adaptive immunity. As part of this process, MHC - II associates with the invariant chain (Ii) during biosynthesis in the endoplasmic reticulum to prevent premature peptide loading and to serve as a scaffold for subsequent proteolytic processing into MHC - II - CLIP. Cryo-electron microscopy structures of full - length Human Leukocyte Antigen - DR (HLA - DR) and HLA - DQ complexes associated with Ii, resolved at 3.0 to 3.1 & Aring;, elucidate the trimeric assembly of the HLA/Ii complex and define atomic - level interactions between HLA, Ii transmembrane domains, loop domains, and class II - associated invariant chain peptides (CLIP). Together with previous structures of MHC - II peptide loading intermediates DO and DM, our findings complete the structural path governing class II antigen presentation.