title: Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing.
abstract: Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8(+) T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.
authors: Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
authors: Giora I
authors: GI
authors: Morozov
authors: Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering/National Institutes of Health, Bethesda, MD 20892;
authors: Huaying
authors: H
authors: Zhao
authors: Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
authors: Michael G
authors: MG
authors: Mage
authors: Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
authors: Lisa F
authors: LF
authors: Boyd
authors: Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
authors: Jiansheng
authors: J
authors: Jiang
authors: Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology/National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
authors: Michael A
authors: MA
authors: Dolan
authors: Laboratory of Immunology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993;
authors: Ramesh
authors: R
authors: Venna
authors: Laboratory of Immunology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993;
authors: Michael A
authors: MA
authors: Norcross
authors: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors: Curtis P
authors: CP
authors: McMurtrey
authors: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors: William
authors: W
authors: Hildebrand
authors: Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering/National Institutes of Health, Bethesda, MD 20892;
authors: Peter
authors: P
authors: Schuck
authors: Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
authors: Kannan
authors: K
authors: Natarajan
authors: Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892; dhm@nih.gov.
authors: David H
authors: DH
authors: Margulies
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D004331:Drosophila melanogaster; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000235:genetics / Q000276:immunology*
chemical_list: C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007136:Immunoglobulins; D008565:Membrane Proteins; D010455:Peptides; C454688:TAPBPL protein, human
keywords: SAXS; antigen presentation; major histocompatibility complex; peptide loading; protein interactions