T-Helper epitopes identified within the E6 transforming protein of cervical cancer-associated human papillomavirus type 16

The E6 oncoprotein of human papillomavirus type 16 (HPV16 E6) produced by t umor cells of HPV16-associated cervical carcinoma is poorly immunogenic in patients, but nonetheless is a tumor-specific antigen to which therapeutic vaccine strategies may be directed. To investigate the subunit immunogenici ty of E6 protein at the T-helper cell level, we immunized mice with overlap ping peptides spanning the entire 158 amino acid sequence. Two peptides rec alled a proliferative response in lymph node cells (LNC) from C57BL/6 (H-2( b))-immunized mice. One of these peptides also recalled proliferative respo nses in the context of 5/5 other major histocompatibility complex (MHC) cla ss II haplotypes, indicating a "promiscuous" T-epitope, Minimal consensus m oth analysis identified the epitopes as (60)VYRDGNPYA(68) and (98)GYNKPLCDL L(107). LNC from mice immunized with T-epitope proliferated in response to challenge with whole E6 protein. Immunization with E6 T-epitopes linked to B-epitopes of HPV16 E7 protein elicited specific antibody indicating that T -cells recognizing the T-epitopes provided cognate "help" for B-cells, LNC from mice co-immunized with E6 T-epitope and the major T-helper epitope of HPV16 E7 ((48)DRAHYNI(54)) proliferated comparably when challenged with the peptides individually indicating co-dominance of the two T-epitopes, The f indings have implications for incorporation of E6 into a therapeutic vaccin e.