Keratinocytes efficiently process endogenous antigens for cytotoxic T-cell mediated lysis.
The generation of a robust CD8(+) cytotoxic T lymphocyte (CTL) response is a key feature of many immunotherapeutic strategies against epithelial tumors and virally infected epithelial tissue. However, surprisingly few studies have addressed whether primary epithelial cells, expressing defined endogenous antigens, are good targets for CTL-mediated lysis. Here, we show that primary keratinocytes (KCs), expressing endogenous ovalbumin (OVA) as a transgene, present measurable H-2K(b)/SIINFEKL complexes at the cell surface and are killed by OVA-specific CTL. Target cell lysis was comparable with a more traditional CTL target cell, EL4, and was enhanced by KC pretreatment with interferon-gamma. These results suggest that primary KCs will be susceptible to CTL-mediated apoptosis when endogenous KC antigens are targeted during immunotherapy.
Zhou
Fang
F
The University of Queensland Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Brisbane, Qld, Australia.
Frazer
Ian H
IH
Leggatt
Graham R
GR
D000818:Animals; D000831:Animals, Newborn; D017951:Antigen Presentation / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006183:H-2 Antigens / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007633:Keratins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C110366:OVA-8; D010446:Peptide Fragments; D007633:Keratins; D007371:Interferon-gamma; D010047:Ovalbumin