E7-ONCOPROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-16 EXPRESSED CONSTITUTIVELY IN THE EPIDERMIS HAS NO EFFECT ON E7-SPECIFIC B-REPERTOIRES OR TH-REPERTOIRES OR ON THE IMMUNE-RESPONSE INDUCED OR SUSTAINED AFTER IMMUNIZATION WITH E7-PROTEIN
K. Herd et al., E7-ONCOPROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-16 EXPRESSED CONSTITUTIVELY IN THE EPIDERMIS HAS NO EFFECT ON E7-SPECIFIC B-REPERTOIRES OR TH-REPERTOIRES OR ON THE IMMUNE-RESPONSE INDUCED OR SUSTAINED AFTER IMMUNIZATION WITH E7-PROTEIN, Virology, 231(1), 1997, pp. 155-165
A line of FVB (H-2(q)) mice transgenic for the E6/E7 open reading fram
es of Human Papillomavirus type 16 driven from the alpha-A crystallin
promoter expresses E7 mRNA in lens and skin epithelium. E7 protein is
detectable in adult skin, coinciding with the development or inflammat
ory skin disease, which progresses to papillomata and squamous carcino
mata in some mice. By examining the outcome of parenteral immunization
with E7 protein, we sought to determine whether endogenous expression
of E7 in skin had induced a preexisting immune outcome, i.e., specifi
c immunity or tolerance, or whether the mice remain naive (''ignorant'
') to E7. Our data show that the antibody response to defined E7 B-epi
topes, the proliferative response to Th epitopes, and the delayed-type
hypersensitivity (DTH) response to whole E7 did not differ between gr
oups or young and old E6/E7 transgenic mice (likely having different d
egrees of lifetime exposure to E7 protein) or between E6/E7-transgenic
and nontransgenic parental strain control mice. Although an E7-specif
ic CTL response could not be induced in the H-2(q) background of these
mice, incorporation of a D-b allele into the genome allowed compariso
n of D-b-restricted CTL responses in E6/E7 transgenic and nontransgeni
c mice. Experiments indicated that the E7-immunization-induced CTL res
ponse did not differ significantly between E6/E7 transgenic and nontra
nsgenic mice. We interpret these results to indicate that in spite of
expression of E7 protein in adult skin, E6/E7 transgenic mice remain i
mmunologically naive (ignorant) of E7 epitopes presented by immunizati
on. (C) 1997 Academic Press.