Heat shock protein 90-mediated peptide-selective presentation of cytosolic tumor antigen for direct recognition of tumors by CD4(+) T cells Journal Article


Authors: Tsuji, T.; Matsuzaki, J.; Caballero, O. L.; Jungbluth, A. A.; Ritter, G.; Odunsi, K.; Old, L. J.; Gnjatic, S.
Article Title: Heat shock protein 90-mediated peptide-selective presentation of cytosolic tumor antigen for direct recognition of tumors by CD4(+) T cells
Abstract: Tumor Ag-specific CD4 + T cells play important functions in tumor immunosurveillance, and in certain cases they can directly recognize HLA class II-expressing tumor cells. However, the underlying mechanism of intracellular Ag presentation to CD4 + T cells by tumor cells has not yet been well characterized. We analyzed two naturally occurring human CD4 + T cell lines specific for different peptides from cytosolic tumor Ag NY-ESO-1. Whereas both lines had the same HLA restriction and a similar ability to recognize exogenous NY-ESO-1 protein, only one CD4 + T cell line recognized NY-ESO-1 + HLA class II-expressing melanoma cells. Modulation of Ag processing in melanoma cells using specific molecular inhibitors and small interfering RNA revealed a previously undescribed peptide-selective Ag-presentation pathway by HLA class II + melanoma cells. The presentation required both proteasome and endosomal protease-dependent processing mechanisms, as well as cytosolic heat shock protein 90-mediated chaperoning. Such tumor-specific pathway of endogenous HLA class II Ag presentation is expected to play an important role in immunosurveillance or immunosuppression mediated by various subsets of CD4 + T cells at the tumor local site. Furthermore, targeted activation of tumor-recognizing CD4 + T cells by vaccination or adoptive transfer could be a suitable strategy for enhancing the efficacy of tumor immunotherapy. © 2012 by The American Association of Immunologists, Inc.
Keywords: signal transduction; controlled study; unclassified drug; human cell; cancer immunotherapy; proteasome; ovary cancer; small interfering rna; rna interference; antigen presentation; antigen specificity; molecular recognition; ny eso 1 antigen; hla antigen class 2; cd4+ t lymphocyte; melanoma cell; heat shock protein 90; adoptive transfer; proteinase; cd4 antigen; immune deficiency; immunosurveillance; cytosol; peripheral blood mononuclear cell; endosomal proteinase; allogeneic restriction; hla restriction
Journal Title: Journal of Immunology
Volume: 188
Issue: 8
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2012-04-15
Start Page: 3851
End Page: 3858
Language: English
DOI: 10.4049/jimmunol.1103269
PROVIDER: scopus
PUBMED: 22427632
DOI/URL:
Notes: --- - "Export Date: 4 June 2012" - "CODEN: JOIMA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Sacha Gnjatic
    111 Gnjatic
  2. Achim Jungbluth
    342 Jungbluth
  3. Gerd Ritter
    158 Ritter
  4. Takemasa Tsuji
    14 Tsuji
  5. Lloyd J Old
    386 Old