Presentation of the HPV16E7 protein by skin grafts is insufficient to allow graft rejection in an E7-primed animal.
The E7 transforming protein of Human Papillomavirus type 16 (HPV16) is expressed in the skin of a line of FVB mice transgenic for the E6 and E7 open reading frames of HPV16 driven from the alpha A crystallin promoter (FVB alpha AcryHPV16E6E7). We have transferred skin from FVB alpha AcryHPV16E6E7 mice to naive or E7-primed syngeneic FVB recipients to assess whether the E7 protein of HPV16 can function as a minor transplantation antigen (MTA) and promote skin graft rejection. FVB mice did not reject E7 expressing tail or flank skin grafts. E7 immunized FVB x C57BL/6J mice recipients of FVB alpha-AcryHPV16E6E7 x C57BL/6J skin generated humoral and DTH responses to E7 in vivo and E7-specific CTL precursors in the spleen, but failed to reject E7 expressing tail skin grafts by 100 days posttransfer. Thus although HPV16 E7 + ve mesenchymal and endodermal tumors can be eliminated by an E7-specific immune response, the same protein is unable to act as a MTA and promote graft rejection when expressed in skin cells. Lack of rejection of grafts expressing MTAs such as E7 may be relevant to the immunology of epithelial tumors expressing tumor-specific antigens and to our understanding of the immunology of diseases of the skin.
Dunn
L A
LA
Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
Evander
M
M
Tindle
R W
RW
Bulloch
A L
AL
de Kluyver
R L
RL
Fernando
G J
GJ
Lambert
P F
PF
Frazer
I H
IH
D000818:Animals; D017931:DNA Primers; D004137:Dinitrochlorobenzene / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D006968:Hypersensitivity, Delayed; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology
D017931:DNA Primers; D004137:Dinitrochlorobenzene; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16