Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway

Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3465-70. doi: 10.1073/pnas.1222342110. Epub 2013 Feb 11.

Abstract

Tapasin is an integral component of the peptide-loading complex (PLC) important for efficient peptide loading onto MHC class I molecules. We investigated the function of the tapasin-related protein, TAPBPR. Like tapasin, TAPBPR is widely expressed, IFN-γ-inducible, and binds to MHC class I coupled with β2-microglobulin in the endoplasmic reticulum. In contrast to tapasin, TAPBPR does not bind ERp57 or calreticulin and is not an integral component of the PLC. β2-microglobulin is essential for the association between TAPBPR and MHC class I. However, the association between TAPBPR and MHC class I occurs in the absence of a functional PLC, suggesting peptide is not required. Expression of TAPBPR decreases the rate of MHC class I maturation through the secretory pathway and prolongs the association of MHC class I on the PLC. The TAPBPR:MHC class I complex trafficks through the Golgi apparatus, demonstrating a function of TAPBPR beyond the endoplasmic reticulum/cis-Golgi. The identification of TAPBPR as an additional component of the MHC class I antigen-presentation pathway demonstrates that mechanisms controlling MHC class I expression remain incompletely understood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology*
  • Calnexin / metabolism
  • Calreticulin / metabolism
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / metabolism
  • HEK293 Cells
  • HLA-A Antigens / metabolism
  • HeLa Cells
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunoglobulins / metabolism*
  • Interferon-gamma / pharmacology
  • Kinetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins / metabolism
  • Peptides / immunology
  • Protein Binding / drug effects
  • Protein Disulfide-Isomerases / metabolism
  • Protein Multimerization / drug effects
  • Protein Transport / drug effects
  • beta 2-Microglobulin / metabolism

Substances

  • Calreticulin
  • HLA-A Antigens
  • Histocompatibility Antigens Class I
  • Immunoglobulins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Peptides
  • TAPBPL protein, human
  • beta 2-Microglobulin
  • tapasin
  • Calnexin
  • Interferon-gamma
  • Protein Disulfide-Isomerases
  • PDIA3 protein, human