Differential binding of viral peptides to HLA-A2 alleles. Implications forhuman papillomavirus type 16 E7 peptide-based vaccination against cervicalcarcinoma

Several cancer immune intervention protocols aim at inducing T cell immunit y against antigens presented by HLA-A2, the most common human MHC class I m olecule. in the context of HLA-A*0201, we previously identified two cytotox ic T lymphocyte epitopes (E7(11-20) and E7(86-93)) encoded by the human pap illomavirus type 16 E7 (HPV16 E7) oncoprotein, which is a tumor-specific an tigen for cervical carcinoma. This study reports that the two HPV16 epitope s 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 super type (M. F. Del Guercio et al., J. Immunol. 1995. 154: 685-693). Cervical c arcinoma patients expressing these alleles may benefit from vaccination wit h the two HPV16 E7 peptides. In contrast, none of the peptides tested bound to A*0207 dr A*0208, whereas heterogeneous binding was observed for A*0205 and A*0206. Therefore, the amino acid substitutions that discriminate thes e 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 pe ptides.