Type Specific and Genotype Cross Reactive B Epitopes of the L1 Protein of HPV16 Defined by a Panel of Monoclonal Antibodies

Kulski, Jerzy K.; Sadleir, John W.; Kelsall, Stephen R.; Cicchini, Maria S.; Shellam, Geoffrey; Shi, Peng; Qi, Ying; Galloway, Denise A.; Zhou, Jiang; Frazer, Ian H.

doi:10.1006/viro.1997.9011

Cited by 18 publications

(11 citation statements)

References 15 publications

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“…This sequence is well conserved among high risk HPVs. This sequence is part of the ENVPDDLYIKGSGS sequence described as corresponding to H16.J4 [9] and 8C4, 5A4, and 1D6 MAbs described by Cason et al [5] and part of the GTVGENVPDDLYIK sequence recognized by MC1-10 and MC-34 described by Kulski et al [23]. This position is in agreement with the fact that the reactivity of this MAb was not affected by insertion of a foreign epitope at positions 266/267 and 283/284.…”

Section: Discussionsupporting

confidence: 85%

Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

et al. 2006

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The majority of the neutralizing epitopes of papillomaviruses (PV) are conformation-specific and have not been fully characterised. Studies have, to date, been limited to a few HPV types only. We analysed the epitopes on the major capsid protein (L1) of Human papillomavirus (HPV) type 31 using monoclonal antibodies (MAbs) generated against HPV-31 virus-like particles (VLPs). The type-specific MAbs against HPV-31 were all found to be neutralizing and recognized conformation-dependent epitopes. Two other MAbs directed against a conformational epitope were found to be cross-reactive with other HPV types, and one of them was found to be cross-neutralizing. Cross-reactive antibodies were further investigated using wild-type HPV-16 L1 VLPs and two mutants. The results obtained suggested the existence of a cross-neutralizing conformational epitope at the N-terminal part of the FG loop of the major capsid protein, and the other four cross-reactive MAbs recognized epitopes also located at the N-terminal part of the FG loop.

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Section: Discussionsupporting

confidence: 85%

Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

et al. 2006

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“…Epitope determination was first validated with the H31.D24 MAb that recognized a linear epitope at position 275–279 (DLYIK), similar to the 271–279 sequence (SVPTDLYIK) identified previously using synthetic peptides 41. This DLYIK motif is also part of the conserved linear epitopes described for other crossreacting MAbs 61–63…”

Section: Discussionmentioning

confidence: 93%

Identification of neutralizing conformational epitopes on the human papillomavirus type 31 major capsid protein and functional implications

et al. 2009

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The aim of this study was to characterize the conformational neutralizing epitopes of the major capsid protein of human papillomavirus type 31. Analysis of the epitopes was performed by competitive epitope mapping using 15 anti-HPV31 and by reactivity analysis using a HPV31 mutant with an insertion of a seven-amino acid motif within the FG loop of the capsid protein. Fine mapping of neutralizing conformational epitopes on HPV L1 was analyzed by a new approach using a system displaying a combinatorial library of constrained peptides exposed on E. coli flagella. The findings demonstrate that the HPV31 FG loop is dense in neutralizing epitopes and suggest that HPV31 MAbs bind to overlapping but distinct epitopes on the central part of the FG loop, in agreement with the exposure of the FG loop on the surface of HPV VLPs, and thus confirming that neutralizing antibodies are mainly located on the tip of capsomeres. In addition, we identified a crossreacting and partially crossneutralizing conformational epitope on the relatively well conserved N-terminal part of the FG loop. Moreover, our findings support the hypothesis that there is no correlation between neutralization and the ability of MAbs to inhibit VLP binding to heparan sulfate, and confirm that the blocking of virus attachment to the extracellular matrix is an important mechanism of neutralization.

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“…Synthetic peptides (containing the LYIKG sequence), recombinant L1 protein and VLP‐elicited antibodies recognized the LYIKG amino acid sequence 32. These antibodies also recognized the intact virus from several HPV types, suggesting that the sequence was exposed on viral capsid 32, 37, 38, 39, 40. Furthermore, this sequence is specifically recognized by sera from patients suffering from cervical intraepithelial neoplasia 41…”

Section: Discussionmentioning

confidence: 98%

“…So far the majority of the neutralizing antibodies have been reported as being conformational rather than linear; however, 3 different linear B‐cell epitopes have been recognized in HABP 18294. The first epitope (residue 264 to 278) is identified in native protein 39. The second one (residue 269 to 284) is recognized by monoclonal antibodies capable of identifying HPV‐16 particles in biopsy 32.…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus type 16 and 18 L1 protein peptide binding to VERO and HeLa cells inhibits their VLPs binding

Vera-Bravo

Ocampo

Urquiza

et al. 2003

Intl Journal of Cancer

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Cervical cancer is the fifth most common type of cancer worldwide (around 500,000 new cases diagnosed each year) and the second major cause of cancer related to women's deaths. 1,2 It has been estimated that over 95% of cervical cancer is associated with HPV infection, 3 since many cervical carcinomas and pre-invasive lesions contain human papillomavirus DNA sequences. 4 Papillomaviruses are classified as being low-risk or high-risk, depending on their preferential association with benign or malignant lesions. HPV-16 DNA is found in about 50 -60% of human anogenital carcinomas, HPV 18 in about 20% and other HPV genotypes in a further 15%. There are as yet undefined papillomavirus sequences in about 15% of anogenital carcinomas. 5,6 Papillomaviruses (PVs) are nonenveloped particles, characterized by having an icosahedral capsid of about 55 nm diameter. The capsids are composed of 2 virally encoded proteins (the L1 major and the L2 minor capsid proteins) that migrate on SDS-PAGE at about 55 and 75 kDa, respectively. The papillomavirus L1 major capsid protein (L1) is the most abundant virus-encoded protein, being highly conserved amongst different HPV types, having amino-acid homology as high as 80%. L1 presents the ability to self-assemble in virus-like particles (VLPs). 7,8 Different PVs seem to use the same receptor to enter their host cells. 7,9,10 Trypsin treatment of cells markedly reduced their ability to bind to VLPs, suggesting that a surface cell protein was involved in VLP binding. 11,12 Red blood cell invasion by Plasmodium falciparum merozoites, 13-15 reticulocytes by Plasmodium vivax merozoites 14 and hepatic cells by Hepatitis C virus 16 has shown that specific receptorligand interactions mediate microbe binding to host cells. Using a similar methodology, synthetic 125 I-radio-labeled peptides were thus used in receptor-ligand type binding assays to better pin/point VERO and HeLa cell binding activity from high-risk 16 and 18 type L1 amino acid sequences. VERO and HeLa cell high activity binding peptides (HABPs) showed saturable binding, cell receptors being sensitive to enzyme treatment and the majority of bound peptide being surface-exposed. HABPs specifically bound to 69 and 54 kDa HeLa cell surface membrane protein and inhibited HPV-16 VLP binding to both cells. Furthermore, several HABP residues formed part of the VLP surface, becoming the target for neutralizing antibodies. METHODS Peptide synthesisTwenty-seven sequential 20-mer peptides, corresponding to HPV type 16 L1, 17 and 29 sequential 20-mer peptides, corresponding to HPV 18 L1, 18 were synthesized by solid-phase multiple peptide system. 19,20 MBHA resin (0.7 meq/g), t-Boc amino-acid and low-high cleavage techniques were used. 21 Peptides were analyzed by MALDI-TOF mass spectrometry and reverse phasehigh performance liquid chromatography (RP-HPLC). These synthesized peptides are shown in 1-letter code in Figures 1a,b. An extra Tyr residue was added to a peptide's C-terminus for radiolabeling purposes when such peptide did not contain Tyr...

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Type Specific and Genotype Cross Reactive B Epitopes of the L1 Protein of HPV16 Defined by a Panel of Monoclonal Antibodies

Cited by 18 publications

References 15 publications

Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

Identification of neutralizing conformational epitopes on the human papillomavirus type 31 major capsid protein and functional implications

Human papillomavirus type 16 and 18 L1 protein peptide binding to VERO and HeLa cells inhibits their VLPs binding

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