Designing of CD8(+) and CD8(+)-overlapped CD4(+) epitope vaccine by targeting late and early proteins of human papillomavirus

Kaliamurthi, Satyavani; Selvaraj, Gurudeeban; Kaushik, Aman Chandra; Gu, Ke-Ren; Wei, Dong-Qing

Both MHC class I and II molecules share some superficial similarities and bind to the 9mer peptides. 101 However, vital differences exist between the MHC class I and II molecules. The capped nature of the MHC class I peptide-binding groove with allele-specific pockets does not allow variation in the length of peptides (9mer), which is called register shifting. This is because the peptide-binding groove of MHC class I molecules is closed at each end. In contrast, the peptidebinding groove of MHC class II molecules is open at both ends which allows for binding of more extended peptides (ranging from >15 to 24 AA in length). Sercarz and Maverakis 102 reported that longer peptides have peptide-flanking residues that lie outside of the peptide-binding groove in MHC class II molecules and might interact with peptides in another distal location. MHC class II proteins primarily present peptides derived from endocytosis of extracellular proteins (exogenous processing pathway). In the present study, promising 15mer CD4 + epitopes were predicted by consensus approaches from the late and early proteins of HPV45. The predicted CD4 + epitopes possessed good binding affinity (<1% lowest percentile rank) for MHC class II alleles. CD4 + immune responses are associated with the production of IFN-γ or IL-2. Furthermore, the IFN-γ-producing CD4 + epitopes were found by using machine learning hybrid method. B cell-mediated humoral immunity involves the recognition of antigens circulating in the body fluid. Recently, Paolini et al 103 reported the production of CD8 + and CD4 + lymphocytes induced by anticancer pVAX-E5CP and pVAX-E5MultiCP E5 vaccine (carrying the whole E5 gene or multi-epitope) in the preclinical cancer model. Bristo et al 104 reported that immunization with a single peptide that contained both the CD4 + and CD8 + CTL epitopes (ie, 9mer CD8 + MHC class I-restricted peptides nested within the 13mer CD4 + epitopes) elicited the response and production of T cells in an animal model. We also predicted the CD8 + -overlapped (9mer) epitopes within the ideal B-cell (16mer) and CD4 + cell (15mer) epitope regions. The results suggested that the CD8 + , nested CD4 + , or B-cell epitopes may elicit CTL-induced cellular immunity or T cell-induced adaptive immunity or B cellmediated humoral immunity. These identified epitopes from HPV45 may have substantial implications in the peptide vaccine-based immunotherapy.