Analysis of major histocompatibility complex class I folding: Novel insights into intermediate forms

L. C. Simone, A. Tuli, P. D. Simone, X. Wang, Joyce C Solheim

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Folding around a peptide ligand is integral to the antigen presentation function of major histocompatibility complex (MHC) class I molecules. Several lines of evidence indicate that the broadly cross-reactive 34-1-2 antibody is sensitive to folding of the MHC class I peptide-binding groove. Here, we show that peptide-loading complex proteins associated with the murine MHC class I molecule K d are found primarily in association with the 34-1-2 + form. This led us to hypothesize that the 34-1-2 antibody may recognize intermediately, as well as fully, folded MHC class I molecules. To further characterize the form(s) of MHC class I molecules recognized by 34-1-2, we took advantage of its cross-reactivity with L d. Recognition of the open and folded forms of L d by the 64-3-7 and 30-5-7 antibodies, respectively, has been extensively characterized, providing us with parameters against which to compare 34-1-2 reactivity. We found that the 34-1-2 +L d molecules displayed characteristics indicative of incomplete folding, including increased tapasin association, endoplasmic reticulum retention, and instability at the cell surface. Moreover, we show that an L d-specific peptide induced folding of the 34-1-2 +L d intermediate. Altogether, these results yield novel insights into the nature of MHC class I molecules recognized by the 34-1-2 antibody.

Original languageEnglish (US)
Pages (from-to)249-262
Number of pages14
JournalTissue Antigens
Volume79
Issue number4
DOIs
Publication statusPublished - Apr 1 2012

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Keywords

  • Antigen processing and presentation
  • Conformation
  • Epitope
  • Folding intermediate
  • Major histocompatibility complex class I
  • Monoclonal antibody
  • Peptide
  • Tapasin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Genetics

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