HSP90α and HSP90β isoforms selectively modulate MHC class II antigen presentation in B cells

Josetta L. Houlihan, Jennifer J. Metzler, Janice S. Blum

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Two isoforms of heat shock protein (HSP) 90, αand β, are abundantly expressed in the cytoplasm of cells, yet only HSP90α serves as a chaperone to potentiate epitope presentation in the context of MHC class I molecules. By contrast, the role of HSP90 isoforms in MHC class II presentation of exogenous and endogenous Ags remains less clear. Studies here using human B lymphoblasts demonstrate the importance of HSP90α and HSP90β isoforms in selectively regulating class II presentation of the diabetes autoantigen glutamic acid decarboxylase (GAD). Inactivation of HSP90 function using geldanamycin or radicicol inhibited MHC class II presentation of exogenous and endogenous GAD, but did not perturb the presentation of several other intra- and extracellular Ags. Treatment of human B cells with geldanamycin and radicicol did not alter cellular MHC class II expression, but did induce a stress response in these APCs. Yet, cell stress alone failed to perturb MHC class II presentation of GAD. HSP90 was found to associate with select Ags such as GAD in cells and ex vivo. Knockdown of HSP90α or HSP90β expression using small interfering RNA decreased the abundance of each isoform, respectively, but did not affect MHC class II expression or induce a stress response. Notably, disruption of HSP90α or HSP90β expression specifically inhibited class II presentation of the exogenous and endogenous GAD Ag. Precomplexing HSP90 with GAD Ag enhanced exogenous GAD Ag presentation. These results demonstrate a requirement for HSP90α and HSP90β in regulating class II presentation of select Ags.

Original languageEnglish (US)
Pages (from-to)7451-7458
Number of pages8
JournalJournal of Immunology
Volume182
Issue number12
DOIs
StatePublished - Jun 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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