Using random forest to classify linear B-cell epitopes based on amino acid properties and molecular features

ABSTRACTAntisera raised against the avian hepatitis E virus (HEV) capsid protein are cross-reactive with human and swine HEV capsid proteins. In this study, two monoclonal antibodies (MAbs) against the avian HEV capsid protein, namely, 3E8 and 1B5, were shown to cross-react with the swine HEV capsid protein. The motifs involved in binding both MAbs were identified and characterized using phage display biopanning, peptide synthesis, and truncated or mutated protein expression, along with indirect enzyme-linked immunosorbent assay (ELISA) and Western blotting. The results showed that the I/VPHD motif is a necessary core sequence and that P and H are two key amino acids for recognition by MAb 3E8. The VKLYM/TS motif is the minimal amino acid sequence necessary for recognition by MAb 1B5. Cross-reactivity between the two epitopes and antibodies against avian, swine, and human HEVs in sera showed that both epitopes are common to avian, swine, and human HEVs. In addition, amino acid sequence alignment of the capsid proteins revealed that the key motifs of both novel epitopes are the same in HEVs from different animal species, predicting that they may be common to HEV isolates from boars, rabbits, rats, ferrets, mongooses, deer, and camels as well. Protein modeling analysis showed that both epitopes are at least partially exposed on the surface of the HEV capsid protein. Protective capacity analysis demonstrated that the two epitopes are nonprotective against avian HEV infection in chickens. Collectively, these studies characterize two novel linear B-cell epitopes common to avian, swine, and human HEVs, which furthers the understanding of HEV capsid protein antigenic structure.IMPORTANCEMore and more evidence indicates that the host range diversity of hepatitis E virus (HEV) is a global public health concern. A better understanding of the antigenic structure of the HEV capsid protein may improve disease diagnosis and prevention. In this study, binding site mapping and localization as well as the antigenic biology of two novel linear B-cell epitopes common to several different species of HEV were characterized. These findings partially reveal the antigenic structure of the HEV capsid protein and provide potential applications for the development of diagnostics and interventions for HEV infection.

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AmPEP: Sequence-based prediction of antimicrobial peptides using distribution patterns of amino acid properties and random forest

Scientific Reports ◽

10.1038/s41598-018-19752-w ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 48

Author(s):

Pratiti Bhadra ◽

Jielu Yan ◽

Jinyan Li ◽

Simon Fong ◽

Shirley W. I. Siu

Keyword(s):

Amino Acid ◽

Random Forest ◽

Antimicrobial Peptides ◽

Distribution Patterns ◽

Acid Properties ◽

Amino Acid Properties

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Predicting linear B-cell epitopes using amino acid anchoring pair composition

BioData Mining ◽

10.1186/s13040-015-0047-3 ◽

2015 ◽

Vol 8 (1) ◽

Cited By ~ 14

Author(s):

Weike Shen ◽

Yuan Cao ◽

Lei Cha ◽

Xufei Zhang ◽

Xiaomin Ying ◽

...

Keyword(s):

Amino Acid ◽

B Cell ◽

B Cell Epitopes ◽

Pair Composition ◽

Linear B

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Linear B-Cell Epitopes in Human Norovirus GII.4 Capsid Protein Elicit Blockade Antibodies

Vaccines ◽

10.3390/vaccines9010052 ◽

2021 ◽

Vol 9 (1) ◽

pp. 52

Author(s):

Hassan Moeini ◽

Suliman Qadir Afridi ◽

Sainitin Donakonda ◽

Percy A. Knolle ◽

Ulrike Protzer ◽

...

Keyword(s):

B Cell ◽

Capsid Protein ◽

Immune Escape ◽

Solvent Accessibility ◽

Effective Vaccine ◽

Blood Group Antigens ◽

Human Norovirus ◽

B Cell Epitopes ◽

Blocking Rate ◽

Linear B

Human norovirus (HuNoV) is the leading cause of nonbacterial gastroenteritis worldwide with the GII.4 genotype accounting for over 80% of infections. The major capsid protein of GII.4 variants is evolving rapidly, resulting in new epidemic variants with altered antigenic potentials that must be considered for the development of an effective vaccine. In this study, we identify and characterize linear blockade B-cell epitopes in HuNoV GII.4. Five unique linear B-cell epitopes, namely P2A, P2B, P2C, P2D, and P2E, were predicted on the surface-exposed regions of the capsid protein. Evolving of the surface-exposed epitopes over time was found to correlate with the emergence of new GII.4 outbreak variants. Molecular dynamic simulation (MD) analysis and molecular docking revealed that amino acid substitutions in the putative epitopes P2B, P2C, and P2D could be associated with immune escape and the appearance of new GII.4 variants by affecting solvent accessibility and flexibility of the antigenic sites and histo-blood group antigens (HBAG) binding. Testing the synthetic peptides in wild-type mice, epitopes P2B (336–355), P2C (367–384), and P2D (390–400) were recognized as GII.4-specific linear blockade epitopes with the blocking rate of 68, 55 and 28%, respectively. Blocking rate was found to increase to 80% using the pooled serum of epitopes P2B and P2C. These data provide a strategy for expanding the broad blockade potential of vaccines for prevention of NoV infection.

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Mining of linear B cell epitopes of SARS-CoV-2 ORF8 protein from COVID-19 patients

Emerging Microbes & Infections ◽

10.1080/22221751.2021.1931465 ◽

2021 ◽

pp. 1-19

Author(s):

Xiaohui Wang ◽

Joy-Yan Lam ◽

Linlei Chen ◽

Shannon Wing-Ngor Au ◽

Kelvin K. W. To ◽

...

Keyword(s):

B Cell ◽

B Cell Epitopes ◽

Linear B

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Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection

PLoS ONE ◽

10.1371/journal.pone.0149638 ◽

2016 ◽

Vol 11 (2) ◽

pp. e0149638 ◽

Cited By ~ 11

Author(s):

Hui-Jie Yang ◽

Jin-Yong Zhang ◽

Chao Wei ◽

Liu-Yang Yang ◽

Qian-Fei Zuo ◽

...

Keyword(s):

Staphylococcus Aureus ◽

B Cell ◽

Protein C ◽

Transport Protein ◽

B Cell Epitopes ◽

Aureus Infection ◽

Manganese Transport ◽

Linear B

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Anaplasma marginale Major Surface Protein 2 CD4+-T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR

Infection and Immunity ◽

10.1128/iai.72.12.7360-7366.2004 ◽

2004 ◽

Vol 72 (12) ◽

pp. 7360-7366 ◽

Cited By ~ 35

Author(s):

Jeffrey R. Abbott ◽

Guy H. Palmer ◽

Chris J. Howard ◽

Jayne C. Hope ◽

Wendy C. Brown

Keyword(s):

T Cell ◽

B Cell ◽

Surface Protein ◽

Anaplasma Marginale ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

Major Surface Protein ◽

Hypervariable Regions ◽

Major Surface ◽

Linear B

ABSTRACT Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4+ T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.

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