Hsp72-mediated augmentation of MHC class I surface expression and endogenous antigen presentation

Andrew D. Wells, Sharath K. Rai, Maria S. Salvato, Hamid Band, Miroslav Malkovsky

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Efficient recognition of tumor cells by cytolytic T lymphocytes (CTL) is often dependent on the presentation of cytosolic peptides in the context of MHC class I molecules. This process may be influenced by various molecular chaperones. To analyze this influence, we have utilized B16 melanoma cells, which are not effectively recognized by MHC class I-restricted CTL. This resistance to CTL is apparently due to a very low level of surface MHC expression. We have found that stably transfected clones of B16 which constitutively express the human heat shock protein 72 (Hsp72) exhibit significantly increased levels of MHC class I antigens on their surface. This Hsp72-mediated up-regulation of surface MHC class I antigen represents an increase in the amount of functional MHC-peptide complexes as measured by conformation-dependent antibodies and recognition by MHC class I-restricted CTL. Expression of Hsp72 did not improve the antigen presentation defect in cells lacking the activity of the transporter associated with antigen presentation (TAP). Moreover, mice immunized with Hsp72-expressing B16 cells, but not with control-transfected B16 cells, display significantly increased resistance to a subsequent challenge with live, wild-type B16. Together, our data demonstrate that the immune recognition of tumor cells can be substantially enhanced by the suitable expression of a molecular chaperone.

Original languageEnglish (US)
Pages (from-to)609-617
Number of pages9
JournalInternational Immunology
Volume10
Issue number5
DOIs
StatePublished - 1998

Keywords

  • Major histocompatibility antigens
  • Molecular chaperone
  • T lymphocytes
  • Tumor immunogenicity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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