HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells.
HPV-16 is the major causes of cervical cancer. Persistence of infection is a necessary event for progression of the infection to cancer. Among other factors, virus persistence is due the viral proteins fighting the immune response. HPV-16 E5 down-regulates MHC/HLA class I, which is much reduced on the cell surface and accumulates in the Golgi apparatus in cells expressing E5. This effect is observed also in W12 cells, which mimic early cervical intraepithelial progression to cervical cancer. The functional effect of MHC I down-regulation on human CD8 T cells is not known, because of the need for HLA-matched, HPV-specific T cells that recognise E5 expressing-cells. Here we employ a heterologous cell/MHC I system which uses mouse cells expressing both E5 and HLA-A2, and A2-restricted CTLs; we show that the E5-induced reduction of HLA-A2 has a functional impact by reducing recognition of E5 expressing cells by HPV specific CD8+ T cells.
Campo
M S
MS
Institute of Comparative Medicine, Division of Pathological Sciences, University of Glasgow, Glasgow, Scotland. s.campo@vet.gla.ac.uk
Graham
S V
SV
Cortese
M S
MS
Ashrafi
G H
GH
Araibi
E H
EH
Dornan
E S
ES
Miners
K
K
Nunes
C
C
Man
S
S
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000096:biosynthesis* / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D007150:Immunohistochemistry; D051379:Mice; D009856:Oncogene Proteins, Viral; D000086082:Viroporin Proteins
D015789:HLA-A2 Antigen; D009856:Oncogene Proteins, Viral; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins