Differential MHC class II component expression in HPV-positive cervical cancer cells: implication for immune surveillance.
Effective eradication of human papillomavirus (HPV)-positive tumors may require CD8+ and CD4+ T-cell-mediated immune responses. Ectopic expression of MHC class II surface molecules has been described in the context of cervical cancer, but coexpression with other components of the MHC class II antigen presentation pathway has not been addressed. We have evaluated the MHC class II antigen presentation pathway in malignant squamous epithelium of HPV+ cervical cancer lesions by in situ costaining HLA-DR with CLIP or DMA/DMB. Cervical cancer cells exhibit 3 MHC class II phenotypes: (i) DR+/CLIP+ or DM+; (ii) DR+/CLIP- or DM-; and (iii) DR-/CLIP+ or DM+. The identical profile has been identified in HPV+ ME180 cells, which serve as a target for HLA-DR4-restricted and HPV68, E7-specific CD4+ T cells. IFN-gamma pretreatment of ME180 cells, associated with differential trafficking of MHC class II molecules, is necessary for effective T-cell recognition. Although proinflammatory cytokines may facilitate MHC class II-restricted antigen recognition in tumor cells, different phenotypes of the MHC class II antigen presentation pathway may be associated with evasion from CD4+-mediated cellular immune responses.
Department of Medical Microbiology, University of Mainz, Mainz, Germany.
Ingeborg
I
Zehbe
Hanni
H
Höhn
Henryk
H
Pilch
Claudia
C
Neukirch
Kirsten
K
Freitag
Markus J
MJ
Maeurer
D001483:Base Sequence; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D027383:Papillomaviridae / Q000302:isolation & purification*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology
D017931:DNA Primers; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma