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TitleStructural insights into human MHC-II association with invariant chain.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 121, Issue 19, Page e2403031121, Year 2024
Publish dateMay 7, 2024
AuthorsNan Wang / Deepa Waghray / Nathanael A Caveney / Kevin M Jude / K Christopher Garcia /
PubMed AbstractThe 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 ...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 Å, 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.
External linksProc Natl Acad Sci U S A / PubMed:38687785 / PubMed Central
MethodsEM (single particle)
Resolution3.03 - 3.12 Å
Structure data

43488

8vrw

EMDB-43488, PDB-8vrw:
Cryo-EM structure of human invariant chain in complex with HLA-DR15
Method: EM (single particle) / Resolution: 3.03 Å

43501

8vsp

EMDB-43501, PDB-8vsp:
Cryo-EM structure of human invariant chain in complex with HLA-DQ
Method: EM (single particle) / Resolution: 3.12 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / Antigen presentation / membrane protein / trimeric complex

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