Identification of a human papillomavirus type 16-specific epitope on the C-terminal arm of the major capsid protein L1.
To characterize epitopes on human papillomavirus (HPV) virus-like particles (VLPs), a panel of mutated HPV-16 VLPs was created. Each mutated VLP had residues substituted from HPV-31 or HPV-52 L1 sequences to the HPV-16 L1 backbone. Mutations were created on the HPV-31 and -52 L1 proteins to determine if HPV-16 type-specific recognition could be transferred. Correct folding of the mutated proteins was verified by resistance to trypsin digestion and by binding to one or more conformation-dependent monoclonal antibodies. Several of the antibodies tested were found to bind to regions already identified as being important for HPV VLP recognition (loops DE, EF, FG, and HI). Sequences at both ends of the long FG loop (amino acids 260 to 290) were required for both H16.V5 and H16.E70 reactivity. A new antibody-binding site was discovered on the C-terminal arm of L1 between positions 427 and 445. Recognition of these residues by the H16.U4 antibody suggests that this region is surface exposed and supports a recently proposed molecular model of HPV VLPs.
Carter
Joseph J
JJ
Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. jcarter@fhcrc.org
Wipf
Greg C
GC
Benki
Sarah F
SF
Christensen
Neil D
ND
Galloway
Denise A
DA
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000145:classification / Q000276:immunology*; D011487:Protein Conformation; D017510:Protein Folding; D011995:Recombination, Genetic; D014771:Virion / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16