The association of an HPV16 oncogene variant with HLA-B7 has implications for vaccine design in cervical cancer.
HLA-restricted cytotoxic T-lymphocyte (CTL) recognition of human papillomavirus (HPV) oncogene products may be important in the control of the HPV infections associated with the development of cervical cancer. We have identified, in HLA-B7 individuals, a consistent variation in the HPV16 E6 oncoprotein sequence, which alters an HLA-B7 peptide binding epitope in a way likely to influence immune recognition by CTLs. These results illustrate a biologically relevant mechanism for escape from immune surveillance of HPV16 in HLA-B7 individuals. Thus, both HLA type and HPV16 strain variation need to be considered in the screening of at-risk individuals and for the rational design of anti-HPV vaccines.
Ellis
J R
JR
University of Birmingham CRC Institute for Cancer Studies, University of Birmingham Medical School, UK.
Keating
P J
PJ
Baird
J
J
Hounsell
E F
EF
Renouf
D V
DV
Rowe
M
M
Hopkins
D
D
Duggan-Keen
M F
MF
Bartholomew
J S
JS
Young
L S
LS
D000595:Amino Acid Sequence; D000939:Epitopes / Q000032:analysis; D005260:Female; D015793:HLA-B7 Antigen / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000628:therapy; D014765:Viral Vaccines / Q000276:immunology*
C068651:E6 protein, Human papillomavirus type 16; D000939:Epitopes; D015793:HLA-B7 Antigen; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D014157:Transcription Factors; D014765:Viral Vaccines