Clustering of peptide-loaded MHC class I molecules for endoplasmic reticulum export imaged by fluorescence resonance energy transfer

Tsvetelina Pentcheva, Michael A Edidin

Research output: Contribution to journalArticle

Abstract

Fluorescence resonance energy transfer between cyan fluorescent protein- and yellow fluorescent protein-tagged MHC class I molecules reports on their spatial organization during assembly and export from the endoplasmic reticulum (ER). A fraction of MHC class I molecules is clustered in the ER at steady state. Contrary to expectations from biochemical models, this fraction is not bound to the TAP. Instead, it appears that MHC class I molecules cluster after peptide loading. This clustering points toward a novel step involved in the selective export of peptide-loaded MHC class I molecules from the ER. Consistent with this model, we detected clusters of wild-type HLA-A2 molecules and of mutant A2-T134K molecules that cannot bind TAP, but HLA-A2 did not detectably cluster with A2-T134K at steady state. Lactacystin treatment disrupted the HLA-A2 clusters, but had no effect on the A2-T134K clusters. However, when cells were fed peptides with high affinity for HLA-A2, mixed clusters containing both HLA-A2 and A2-T134K were detected.

Original languageEnglish (US)
Pages (from-to)6625-6632
Number of pages8
JournalJournal of Immunology
Volume166
Issue number11
StatePublished - May 1 2001

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HLA-A2 Antigen
Fluorescence Resonance Energy Transfer
Endoplasmic Reticulum
Cluster Analysis
varespladib methyl
Peptides
Proteins

ASJC Scopus subject areas

  • Immunology

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Clustering of peptide-loaded MHC class I molecules for endoplasmic reticulum export imaged by fluorescence resonance energy transfer. / Pentcheva, Tsvetelina; Edidin, Michael A.

In: Journal of Immunology, Vol. 166, No. 11, 01.05.2001, p. 6625-6632.

Research output: Contribution to journalArticle

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