scholarly journals A bioinformatics approach for identifying the probable cause of the cross-interaction of antibodies to the antigenic protein HPV16 L1 with the HPV6 L1 protein

2021 ◽  
Vol 25 (7) ◽  
pp. 787-792
Author(s):  
A. S. Stolbikov ◽  
R. K. Salyaev ◽  
N. I. Rekoslavskaya
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
B Cell ◽  
Antigenic Determinant ◽  
Amino Acid Sequences ◽  
Antigenic Determinants ◽  
Antigenic Protein ◽  
Hpv Types ◽  
The Cross

This paper describes an attempt to analyze, with the aid of bioinformatics resources (programs and databases), the probable cause of the cross-interaction of antibodies against HPV16 L1 with antigenic protein HPV6 L1, which has been revealed in the investigation of the candidate vaccine obtained on the base of a plant expression system (tomato plants). In our opinion, the most likely reason for the cross-interaction of antibodies with antigens of different pathogenic HPV types is the similarity of their antigenic determinants. In this work, the amino acid sequences of HPV16 L1 and HPV6 L1 used for the development of a binary vaccine against cervical cancer and anogenital papillomatosis have been analyzed. For the analysis of antigenic determinants, the programs BepiPred-2.0: Sequential B-Cell Epitope Predictor, DiscoTope 2.0 Server and SYFPEITHI have been used. As a result of the analysis of probable B-cell linear determinants (epitopes), it has been found that in both types of HPV the proteins have approximately the same location and size of linear antigenic determinants; the difference is observed only in the form of small shifts in the size of several amino acid residues. However, there are some differences in the amino acid composition of epitopes; therefore, the possibility for cross-interaction of the antibodies with the antigens due to the similarity of linear antigenic determinants for B-cells is very small. The analysis of potential threedimensional epitopes for B-cells has shown that due to little difference between them the HPV16 L1 and HPV6 L1 proteins have no prerequisites for cross-interaction of the antibodies with the antigens belonging to the two different pathogenic HPV types. The analysis of probable linear epitopes for T-cells has revealed a common antigenic determinant in the two protein sequences. According to the rank made with the SYFPEITHI program, the amino acid sequence AQL(I)FNKPYWL is the second most likely antigenic determinant for T-cells. Meanwhile, the amino acid sequences of this determinant in HPV16 L1 and HPV6 L1 are virtually identical. There is a difference in only one position, but it is not critical due to the similarity of the physicochemical properties of amino acids, for which there is a replacement in the amino acid sequence of antigenic determinants. Consequently, some moderate cross-interaction of the antibodies to HPV16 L1 with the antigens of HPV6 L1 may be expected.

scholarly journals Biochemical and Immunological Characterization of MP65, a Major Mannoprotein Antigen of the Opportunistic Human PathogenCandida albicans

2000 ◽  
Vol 68 (2) ◽  
pp. 694-701 ◽  
Author(s):  
Maria J. Gomez ◽  
Bruno Maras ◽  
Alessandra Barca ◽  
Roberto La Valle ◽  
Donatella Barra ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Synthetic Peptides ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Amino Acid Sequences ◽  
Antigenic Determinants ◽  
Cell Mediated Immunity ◽  
Antigenic Peptides

ABSTRACT In the search of the antigenic determinants of a 65-kDa mannoprotein (MP65) of Candida albicans, tryptic fragments of immunoaffinity-purified MP65 preparations were tested for their ability to induce lymphoproliferation of human peripheral blood mononuclear cells (PBMC). Five major peptides (T1 to T5) were shown to induce a vigorous proliferation of PBMC from the majority of the eight healthy human subjects tested. With the use of synthetic peptides, critical amino acid sequences of the two most immunoactive (T1 and T2) peptides were determined. Similar to what was found for the MP65 molecule, no PBMC multiplication was induced by the antigenic peptides in cultures of naive cord blood cells. The amino acid sequence analysis of tryptic and chymotryptic peptides of MP65 demonstrated a substantial homology with the deduced sequences of two cell wall proteins ofSaccharomyces cerevisiae, encoded by the genesYRM305C and YGR279C. However, the antigenic peptides were those showing the least similarity with the corresponding regions of the above proteins. In particular, the lymphoproliferation-inducing sequence of the T1 peptide scored only 20% identity with the homologous regions of S. cerevisiaeproteins. Besides disclosing the amino acid sequence of MP65, this study provides an initial characterization of some of its antigenic determinants, as well as of synthetic peptides of potential use to detect specific immune responses against MP65, a major target of anticandidal cell-mediated immunity in humans.

scholarly journals The amino acid sequence of cytochromes c-551 from three species of Pseudomonas

1973 ◽  
Vol 131 (3) ◽  
pp. 485-498 ◽  
Author(s):  
R. P. Ambler ◽  
Margaret Wynn
Keyword(s):  
Amino Acids ◽  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Cytochrome C ◽  
Amino Acid Sequence ◽  
Amino Acid Sequences ◽  
Mitochondrial Cytochrome ◽  
Cytochromes C ◽  
Lending Library ◽  
Single Peptide

The amino acid sequences of the cytochromes c-551 from three species of Pseudomonas have been determined. Each resembles the protein from Pseudomonas strain P6009 (now known to be Pseudomonas aeruginosa, not Pseudomonas fluorescens) in containing 82 amino acids in a single peptide chain, with a haem group covalently attached to cysteine residues 12 and 15. In all four sequences 43 residues are identical. Although by bacteriological criteria the organisms are closely related, the differences between pairs of sequences range from 22% to 39%. These values should be compared with the differences in the sequence of mitochondrial cytochrome c between mammals and amphibians (about 18%) or between mammals and insects (about 33%). Detailed evidence for the amino acid sequences of the proteins has been deposited as Supplementary Publication SUP 50015 at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973), 131, 5.

scholarly journals Factor D̄ of the alternative pathway of human complement. Purification, alignment and N-terminal amino acid sequences of the major cyanogen bromide fragments, and localization of the serine residue at the active site

1980 ◽  
Vol 187 (3) ◽  
pp. 863-874 ◽  
Author(s):  
D M Johnson ◽  
J Gagnon ◽  
K B Reid
Keyword(s):  
Amino Acid ◽  
Sequence Analysis ◽  
Amino Acid Sequence ◽  
Alternative Pathway ◽  
Amino Acid Sequences ◽  
Serine Residue ◽  
Amino Acid Sequence Analysis ◽  
Terminal Amino Acid ◽  
Terminal Amino ◽  
Terminal Amino Acid Sequence

The serine esterase factor D of the complement system was purified from outdated human plasma with a yield of 20% of the initial haemolytic activity found in serum. This represented an approx. 60 000-fold purification. The final product was homogeneous as judged by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis (with an apparent mol.wt. of 24 000), its migration as a single component in a variety of fractionation procedures based on size and charge, and its N-terminal amino-acid-sequence analysis. The N-terminal amino acid sequence of the first 36 residues of the intact molecule was found to be homologous with the N-terminal amino acid sequences of the catalytic chains of other serine esterases. Factor D showed an especially strong homology (greater than 60% identity) with rat ‘group-specific protease’ [Woodbury, Katunuma, Kobayashi, Titani, & Neurath (1978) Biochemistry 17, 811-819] over the first 16 amino acid residues. This similarity is of interest since it is considered that both enzymes may be synthesized in their active, rather than zymogen, forms. The three major CNBr fragments of factor D, which had apparent mol.wts. of 15 800, 6600 and 1700, were purified and then aligned by N-terminal amino acid sequence analysis and amino acid analysis. By using factor D labelled with di-[1,3-14C]isopropylphosphofluoridate it was shown that the CNBr fragment of apparent mol.wt. 6600, which is located in the C-terminal region of factor D, contained the active serine residue. The amino acid sequence around this residue was determined.

Die primäre Proteinstruktur von Stämmen des Tabakmosaikvirus

1963 ◽  
Vol 18 (12) ◽  
pp. 1032-1049 ◽  
Author(s):  
B. Wittmann-Liebold ◽  
H. G. Wittmann
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Amino Acid Sequences ◽  
Tryptic Peptides

The amino acid sequence of dahlemense, a naturally occuring strain of tobacco mosaic virus, has been determined and compared with that of the strain vulgare (Fig. 7). In this communication the experimental details are given for the elucidation of the amino acid sequences within two tryptic peptides with 65 amino acids.

scholarly journals A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Intravenous Doses of IGN002 Administered Weekly to Subjects with Refractory Non-Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-35
Author(s):  
Patricia A. Young ◽  
Fabio D Mataveli
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
B Cell ◽  
Dose Escalation ◽  
Phase 1 ◽  
Open Label ◽  
Free Interval ◽  
Period 2 ◽  
Expansion Stage ◽  
Anti Cd20

Background:Non-Hodgkin lymphoma (NHL) is the most common, adult hematologic malignancy. Despite available treatment, relapse rates are high and novel therapies are warranted. IGN002 consists of an anti-CD20 monoclonal antibody (mAb) fused to interferon-alpha (IFNα) via a short peptide linker. The mAb portion of IGN002 is a chimeric IgG1 antibody with the same amino acid sequence as rituximab. The interferon amino acid sequence is human IFNα2b (hIFNα2b). In nonclinical pharmacology studies using CD20-positive human NHL cells, IGN002 demonstrates compelling anti-tumor effects. When compared to rituximab, IGN002 demonstrated enhanced complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) effector functions against CD20-positive NHL cells. Moreover, compared to rituximab against normal human primary B-cells, IGN002 displayed higher maximal and more potent ADCC activity. Finally, in xenograft studies with immunodeficient mice using 3 different human NHL cell lines comparing IGN002 to rituximab, IGN002 demonstrated superior median and overall survival in all 3 NHL xenograft tumor lines. Study Design and Methods :This open-label, non-randomized, first-in-human, dose finding Phase 1 study comprises a Dose-Escalation Stage and an Expansion Stage (NCT02519270). In the Dose-Escalation Stage, ascending dose cohorts will be treated in 2 periods until the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) is identified. In Period 1, subjects will receive 2 doses of IGN002 administered weekly. Subjects with no anti-drug antibodies to IGN002 at Week 6 in Period 1 will proceed to Period 2 and receive up to 24 additional doses of IGN002 administered weekly in three 8-week cycles, with no treatment-free interval. In the Expansion Stage, subjects will receive up to 24 doses of IGN002 at the MTD or RP2D administered weekly in three 8-week cycles, with no treatment-free interval. Cohorts 1-5 at dose level 0.1, 0.3, 1, 3, and 10 ug/kg, respectively, have been completed without any dose limiting toxicity (DLT) and enrollment for Cohorts 6-8 is impending. Clinical Endpoints:The primary outcome measures are the evaluation of safety and tolerability of multiple doses of IGN002 administered weekly as an IV infusion to subjects with refractory NHL and the determination of MTD or RP2D of IGN002. The secondary outcome measures include characterizing the pharmacokinetic profile of ascending doses of IGN002, the incidence of anti-IGN002 antibody formation, and assessment of anti-tumor activity (e.g., response rate, duration) of IGN002 using the Lugano Classification criteria for NHL. Eligibility Criteria:This study is enrolling patients > 18 years with an ECOG <2 who have a documented history of immunohistochemistry-confirmed CD20-positive B-cell NHL, including diffuse large B-cell, mantle cell, marginal zone, lymphoplasmacytic, follicular, transformed follicular, or primary mediastinal B-cell lymphoma that is refractory to at least 1 documented regimen containing rituximab or a similar anti-CD20 therapy. Patients must also have measurable disease and adequate organ function. The exclusionary criteria encompass treatment with an approved or investigational chemotherapy or anti-CD20 drug within 28 days of Day 1, treatment with an approved or investigational biologic drug that does not target CD20 within 90 days of Day 1, or radiation therapy within 4 weeks of Day 1. Statistical Methods:The sample size was not predicated on formal statistical considerations. Descriptive statistics will be used to summarize continuous variables. Dichotomous endpoints will be summarized using frequencies, proportions, and exact binomial 95% CI. For subjects treated at the MTD or RP2D in Period 2 of the Dose-Escalation Stage and the Expansion Stage, time-to-event variables will be summarized using the Kaplan-Meier method. Target Accrual:In the Dose-Escalation Stage and Expansion Stage, approximately 9-18 (~3-6 subjects per cohort) and 14 subjects, respectively, will be accrued. Enrollment for Cohort 6 is expected to commence in September 2020. Disclosures Mataveli: Spectrum Pharmaceuticals:Current Employment, Current equity holder in publicly-traded company.

scholarly journals Diarrhea-Inducing Activity of Avian Rotavirus NSP4 Glycoproteins, Which Differ Greatly from Mammalian Rotavirus NSP4 Glycoproteins in Deduced Amino Acid Sequence, in Suckling Mice

2002 ◽  
Vol 76 (11) ◽  
pp. 5829-5834 ◽  
Author(s):  
Yoshio Mori ◽  
Mohammed Ali Borgan ◽  
Naoto Ito ◽  
Makoto Sugiyama ◽  
Nobuyuki Minamoto
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Amino Acid Sequences ◽  
Amino Acid Residues ◽  
Suckling Mice

ABSTRACT Avian rotavirus NSP4 glycoproteins expressed in Escherichia coli acted as enterotoxins in suckling mice, as did mammalian rotavirus NSP4 glycoproteins, despite great differences in the amino acid sequences. The enterotoxin domain of PO-13 NSP4 exists in amino acid residues 109 to 135, a region similar to that reported in SA11 NSP4.

scholarly journals Nucleotide and derived amino acid sequences of a cDNA coding for pre-uteroglobin from the lung of the hare (Lepus capensis)

1986 ◽  
Vol 235 (3) ◽  
pp. 895-898 ◽  
Author(s):  
M S López de Haro ◽  
A Nieto
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Nucleotide Sequence ◽  
Amino Acid Sequence ◽  
Amino Acid Sequences ◽  
Untranslated Regions ◽  
Coding Region ◽  
Homologous Proteins ◽  
Lepus Capensis ◽  
Rabbit Gene

An almost full-length cDNA coding for pre-uteroglobin from hare lung was cloned and sequenced. The derived amino acid sequence indicated that hare pre-uteroglobin contained 91 amino acids, including a signal peptide of 21 residues. Comparison of the nucleotide sequence of hare pre-uteroglobin cDNA with that previously reported for the rabbit gene indicated five silent point substitutions and six others leading to amino acid changes in the coding region. The untranslated regions of both pre-uteroglobin mRNAs were very similar. The amino acid changes observed are discussed in relation to the different progesterone-binding abilities of both homologous proteins.

scholarly journals Structural gene and complete amino acid sequence of Vibrio alginolyticus collagenase

1992 ◽  
Vol 281 (3) ◽  
pp. 703-708 ◽  
Author(s):  
H Takeuchi ◽  
Y Shibano ◽  
K Morihara ◽  
J Fukushima ◽  
S Inami ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nucleotide Sequence ◽  
Amino Acid Sequence ◽  
Structural Gene ◽  
Sequence Similarity ◽  
Vibrio Alginolyticus ◽  
Amino Acid Sequences ◽  
Dna Encoding ◽  
Cloned Gene ◽  
Collagenase Gene

The DNA encoding the collagenase of Vibrio alginolyticus was cloned, and its complete nucleotide sequence was determined. When the cloned gene was ligated to pUC18, the Escherichia coli expression vector, bacteria carrying the gene exhibited both collagenase antigen and collagenase activity. The open reading frame from the ATG initiation codon was 2442 bp in length for the collagenase structural gene. The amino acid sequence, deduced from the nucleotide sequence, revealed that the mature collagenase consists of 739 amino acids with an Mr of 81875. The amino acid sequences of 20 polypeptide fragments were completely identical with the deduced amino acid sequences of the collagenase gene. The amino acid composition predicted from the DNA sequence was similar to the chemically determined composition of purified collagenase reported previously. The analyses of both the DNA and amino acid sequences of the collagenase gene were rigorously performed, but we could not detect any significant sequence similarity to other collagenases.

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