Structural insights into human MHC-II association with invariant chain.

Nan Wang, Deepa Waghray, Nathanael A Caveney, Kevin M Jude, K Christopher Garcia

Proceedings of the National Academy of Sciences of the United States of America 2024 May 07

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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.

Citation

Nan Wang, Deepa Waghray, Nathanael A Caveney, Kevin M Jude, K Christopher Garcia. Structural insights into human MHC-II association with invariant chain. Proceedings of the National Academy of Sciences of the United States of America. 2024 May 07;121(19):e2403031121