Invariant Chain Association with MHC Class I: Preference for HLA Class 1/β2-Microglobulin Heterodimers, Specificity, and Influence of the MHC Peptide-Binding Groove

Janet L. Vigna, Kelly D. Smith, Charles T. Lutz

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

MHC class I molecules require the assembly of heavy chain with β2-microglobulin (β2m) and peptide in order to present Ag on the cell surface. Endoplasmic reticulum resident proteins associate with class I molecules and aid assembly. Free class I heavy chains associate with calnexin, which may facilitate association with β2m. Invariant chain (Ii) also associates with MHC class I molecules, but its role in class I assembly is not clear. We report here that Ii strongly associates with HLA class 1/β2m heterodimers, but weakly with free class I heavy chains in HLA-B7-transfected T2 cells. Ii/HLA class I complexes persist stably within the endoplasmic reticulum/cis-Golgi compartment in peptide-processing deficient cells, but are much less prominent in normally processing cells. Furthermore, Ii differentially associates with variant HLA-B7 molecules that have peptide-binding groove mutations, and the degree of association correlates with HLA-B7 variant cell surface expression. Ii also shows HLA class I molecule specificity, associating to a greater degree with HLA-B7 than HLA-A2. Together these observations suggest that Ii stabilizes particular HLA class 1/β2m heterodimers until peptide is loaded, and that this association may enhance class I cell surface expression.

Original languageEnglish
Pages (from-to)4503-4510
Number of pages8
JournalJournal of Immunology
Volume157
Issue number10
StatePublished - Nov 15 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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