2. Academic Validation
  3. Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

  • Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E1006-15. doi: 10.1073/pnas.1519894113.
Giora I Morozov 1,  Huaying Zhao 2,  Michael G Mage 1,  Lisa F Boyd 1,  Jiansheng Jiang 1,  Michael A Dolan 3,  Ramesh Venna 4,  Michael A Norcross 4,  Curtis P McMurtrey 5,  William Hildebrand 5,  Peter Schuck 2,  Kannan Natarajan 1,  David H Margulies 6
Affiliations

Affiliations

  • 1 Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
  • 2 Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering/National Institutes of Health, Bethesda, MD 20892;
  • 3 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;
  • 4 Laboratory of Immunology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993;
  • 5 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
  • 6 Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892; dhm@nih.gov.
PMID: 26869717 DOI: 10.1073/pnas.1519894113
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.

Keywords

SAXS; antigen presentation; major histocompatibility complex; peptide loading; protein interactions.

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