T-HELPER EPITOPES OF THE E7 TRANSFORMING PROTEIN OF CERVICAL-CANCER ASSOCIATED HUMAN PAPILLOMAVIRUS TYPE-18 (HPV18)

The presence of T-helper epitopes within the E7 transforming protein of human papillomavirus type 18 (HPV18) was sought using a series of overlapping synthetic 15-20 mer peptides spanning the entire 105 amino acid sequence of this protein. Two H-2(k) restricted T-helper epitopes were defined, comprising (44)VNHQHLPARRA(55) and (81)DDLRAFQQLF(90) as the minimal T proliferative epitopes. Peptides containing these epitopes were able to provide cognate help to B epitopes from HPV18E7 protein for production of antibody to this protein in vivo in CBA/CaH mice. No H-2(b) or H-2(d) restricted epitopes were demonstrable, and in H-2(d) mice this was associated with poor antibody response to the E7 protein. There is no ''promiscuous'' T-helper epitope in HPV18 E7 comparable to the (49)DRAHYNI(55) sequence in HPV16 E7, and restricted T-helper epitope availability may be a determinant of poor immune responses to this protein after natural infection.