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
  • 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; [email protected].
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.