Differential binding of viral peptides to HLA-A2 alleles. Implications for human papillomavirus type 16 E7 peptide-based vaccination against cervical carcinoma.
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.
Ressing
M E
ME
Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands.
de Jong
J H
JH
Brandt
R M
RM
Drijfhout
J W
JW
Benckhuijsen
W E
WE
Schreuder
G M
GM
Offringa
R
R
Kast
W M
WM
Melief
C J
CJ
D000483:Alleles; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D005260:Female; D015789:HLA-A2 Antigen / Q000032:analysis / Q000235:genetics*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000276:immunology* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy*; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16