Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain α3 domain

Woong Kyung Suh, Michael A. Derby, Myrna F. Cohen-Doyle, Gary J. Schoenhals, Klaus Früh, Jay A. Berzofsky, David B. Williams

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

In human cells the association of MHC class I molecules with TAP is thought to be mediated by a third protein termed tapasin. We now show that tapasin is present in murine TAP-class I complexes as well. Furthermore, we demonstrate that a mutant H-2D(d) molecule that does not interact with TAP due to a Glu to Lys mutation at residue 222 of the H chain (D(d)(E222K)) also fails to bind to tapasin. This finding supports the view that tapasin bridges the association between class I and TAP and implicates residue 222 as a site of contact with tapasin. The inability of D(d)(E222K) to interact with tapasin and TAP results in impaired peptide loading within the endoplasmic reticulum. However, significant acquisition of peptides can still be detected as assessed by the decay kinetics of cell surface D(d)(E222K) molecules and by the finding that prolonged viral infection accumulates sufficient target structures to stimulate T cells at 50% the level observed with wild-type D(d). Thus, although interaction with tapasin and TAP enhances peptide loading, it is not essential. Finally, a cohort of D(d)(E222K) molecules decays more rapidly on the cell surface compared with wild-type D(d) molecules but much more slowly than peptide-deficient molecules. This suggests that some of the peptides obtained in the absence of an interaction with tapasin and TAP are suboptimal, suggesting a peptide-editing function for tapasin/TAP in addition to their role in enhancing peptide loading.

Original languageEnglish (US)
Pages (from-to)1530-1540
Number of pages11
JournalJournal of Immunology
Volume162
Issue number3
StatePublished - Feb 1 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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