Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation

• Published in: Science (American Association for the Advancement of Science) Vol. 358; no. 6366; pp. 1064 - 1068
• Main Authors: Jiang, Jiansheng, Natarajan, Kannan, Boyd, Lisa F., Morozov, Giora I., Mage, Michael G., Margulies, David H.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 24.11.2017; The American Association for the Advancement of Science; AAAS
• Subjects: Affinity; Antigen Presentation; Antigen-presenting cells; Antigens; BASIC BIOLOGICAL SCIENCES; beta 2-Microglobulin - chemistry; beta 2-Microglobulin - ultrastructure; CD8 antigen; Chaperones; Crystal structure; Crystallography, X-Ray; Cytotoxicity; Editing; Endoplasmic reticulum; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - ultrastructure; Homology; Humans; Immunity; Immunoglobulins - chemistry; Immunoglobulins - ultrastructure; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Membrane Proteins - chemistry; Membrane Proteins - ultrastructure; Peptides; Peptides - chemistry; Protein Conformation; Proteins; Surface Plasmon Resonance; Tapasin
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aao5154

Central to CD8⁺ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.