Cutting edge: cross-presentation of cell-associated antigens to MHC class I molecule is regulated by a major transcription factor for heat shock proteins.
The ability for the professional APC to cross-present Ag to MHC class I from parenchymal cells is essential for priming as well as tolerance of CD8+ T cells against intracellular Ags. Since cross-presentations of non-cell-associated free Ags are inefficient, the roles of molecular chaperones or heat shock proteins (HSPs) in chaperoning Ags to APCs have been postulated. We herein genetically addressed this hypothesis using mice that were defective of heat shock factor 1 (Hsf1), a major transcription factor for HSPs. Hsf1(-/-) mice have a decreased expression of several HSPs including HSP90 and HSP70. Using multiple Ag systems, we demonstrated that cross-priming of Ag-specific CD8+ T cells was inefficient when Ag expression was restricted to Hsf1(-/-) non-APCs. Our study provides the first genetic evidence for the roles of Hsf1 in regulating cross-presentation of MHC class I-associated Ags.
Zheng
Hong
H
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.
Li
Zihai
Z
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002461:Cell Line, Transformed; D002645:Chickens; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004527:Egg Proteins / Q000276:immunology / Q000378:metabolism; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009698:Nucleoproteins / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D004527:Egg Proteins; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; D007252:Influenza Vaccines; D009698:Nucleoproteins; C110366:OVA-8; D010446:Peptide Fragments; D014157:Transcription Factors; C122116:nucleoprotein (147-155); D010047:Ovalbumin