Differential binding of viral peptides to HLA-A2 alleles. Implications for human papillomavirus type 16 E7 peptide-based vaccination against cervical carcinoma

Abstract

Several cancer immune intervention protocols aim at inducing T cell immunity against antigens presented by HLA‐A2, the most common human MHC class I molecule. In the context of HLA‐A*0201, we previously identified two cytotoxic T lymphocyte epitopes (E7_{11 – 20} and E7_{86 – 93}) encoded by the human papillomavirus type 16 E7 (HPV16 E7) oncoprotein, which is a tumor‐specific antigen for cervical carcinoma. This study reports that the two HPV16 epitopes and a control hepatitis B virus epitope bind equally well to five HLA‐A2 alleles (A*0201, A*0202, A*0203, A*0204, and A*0209). These HLA‐A2 variants display comparable binding characteristics in accordance with the A2 supertype (M. F. Del Guercio et al., J. Immunol. 1995. 154: 685 – 693). Cervical carcinoma patients expressing these alleles may benefit from vaccination with the two HPV16 E7 peptides. In contrast, none of the peptides tested bound to A*0207 or A*0208, whereas heterogeneous binding was observed for A*0205 and A*0206. Therefore, the amino acid substitutions that discriminate these HLA‐A2 variants from A*0201 affect antigen presentation. Taken together, our findings have implications for application of the A2 supertype concept and for vaccination with A*0201‐binding peptides, in particular HPV16 E7 peptides.