PRESENTATION OF THE HPV16E7 PROTEIN BY SKIN-GRAFTS IS INSUFFICIENT TOALLOW 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 RIB mice transgenic for the E6 and E7 open reading frames of HPV16 driven from the alpha A crystallin pr omoter (FVB alpha AcryHPV16E6E7). We have transferred skin from FVB al pha AcryHPV16E6E7 mice to naive or E7-primed syngeneic NE recipients t o assess whether the E7 protein of HPV16 can function as a minor trans plantation antigen (MTA) and promote skin graft rejection. FVB mice di d 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 57 expressing tail ski n grafts by 100 days posttransfer. Thus although HPV16 E7 + ve mesench ymal 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 e xpressing MTAs such as E7 may be relevant to the immunology of epithel ial tumors expressing tumor-specific antigens and to our understanding of the immunology of diseases of the skin. (C) 1997 Academic Press.