Influence of the tapasin C terminus on the assembly of MHC class i allotypes

Laura C. Simone, Xiaojian Wang, Amit Tuli, Mary M. McIlhaney, Joyce C Solheim

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Several endoplasmic reticulum proteins, including tapasin, play an important role in major histocompatibility complex (MHC) class I assembly. In this study, we assessed the influence of the tapasin cytoplasmic tail on three mouse MHC class I allotypes (H2-Kb, -Kd, and -L d) and demonstrated that the expression of truncated mouse tapasin in mouse cells resulted in very low Kb, Kd, and L d surface expression. The surface expression of Kd also could not be rescued by human soluble tapasin, suggesting that the surface expression phenotype of the mouse MHC class I molecules in the presence of soluble tapasin was not due to mouse/human differences in tapasin. Notably, soluble mouse tapasin was able to partially rescue HLA-B8 surface expression on human 721.220 cells. Thus, the cytoplasmic tail of tapasin (either mouse or human) has a stronger impact on the surface expression of murine MHC class I molecules on mouse cells than on the expression of HLA-B8 on human cells. A K408W mutation in the mouse tapasin transmembrane/cytoplasmic domain disrupted Kd folding and release from tapasin, but not interaction with transporter associated with antigen processing (TAP), indicating that the mechanism whereby the tapasin transmembrane/cytoplasmic domain facilitates MHC class I assembly is not limited to TAP stabilization. Our findings indicate that the C terminus of mouse tapasin plays a vital role in enabling murine MHC class I molecules to be expressed at the surface of mouse cells.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalImmunogenetics
Volume61
Issue number1
DOIs
Publication statusPublished - Jan 1 2009

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Keywords

  • Antigen presentation
  • Antigen processing
  • Major histocompatibility complex
  • Mouse
  • Tapasin

ASJC Scopus subject areas

  • Immunology
  • Genetics

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