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

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:
 [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [3] ;  [4] ;  [4] ;  [5] ;  [5] ;  [2] ;  [1] ;  [1]
  1. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases. Lab. of Immunology. Molecular Biology Section
  2. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Biomedical Imaging and Bioengineering. Lab. of Cellular Imaging and Macromolecular Biophysics
  3. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases. Office of Cyber Infrastructure and Computational Biology. Bioinformatics and Computational Biosciences Branch
  4. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research. Lab. of Immunology
  5. Univ. of Oklahoma Health Sciences Center, Oklahoma City, OK (United States). Dept. of Microbiology and Immunology
Publication Date:
OSTI Identifier:
1242290
Grant/Contract Number:
AC02-06CH11357; 9 P41 GM103622; AI0000394; EB000008; 1617
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 113; Journal Issue: 8; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
National Inst. of Health (NIH), Bethesda, MD (United States)
Sponsoring Org:
USDOE Office of Science (SC); National Inst. of Health (NIH) (United States)
Contributing Orgs:
Food and Drug Administration (FDA), Silver Spring, MD (United States); Univ. of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; antigen presentation; peptide loading; major histocompatibility complex; protein interactions; SAXS