title: Predicting promiscuous antigenic T cell epitopes of Mycobacterium tuberculosis mymA operon proteins binding to MHC Class I and Class II molecules.
abstract: Limited efficacy of Bacillus Calmette-Guérin vaccine has raised the need to explore other immunogenic candidates to develop an effective vaccine against Mycobacterium tuberculosis (Mtb). Both CD4+ and CD8+ T cells play a critical role in host immunity to Mtb. Infection of macrophages with Mtb results in upregulation of mymA operon genes thereby suggesting their importance as immune targets. In the present study, after exclusion of self-peptides mymA operon proteins of Mtb were analyzed in silico for the presence of Human Leukocyte Antigen (HLA) Class I and Class II binding peptides using Bioinformatics and molecular analysis section, NetMHC 3.4, ProPred and Immune epitope database software. Out of 56 promiscuous epitopes obtained, 41 epitopes were predicted to be antigenic for MHC Class I. In MHC Class II, out of 336 promiscuous epitopes obtained, 142 epitopes were predicted to be antigenic. The comparative bioinformatics analysis of mymA operon proteins found Rv3083 to be the best vaccine candidate. Molecular docking was performed with the most antigenic peptides of Rv3083 (LASGAASVV with alleles HLA-B51:01, HAATSGTLI with HLA-A02, IVTATGLNI and EKIHYGLKVNTA with HLA-DRB1_01:01) to study the structural basis for recognition of peptides by various HLA molecules. The software binding prediction was validated by the obtained molecular docking score of peptide-HLA complex. These peptides can be further investigated for their immunological relevance in patients of tuberculosis using major histocompatibility complex tetramer approach.
authors.affiliation: D S Kothari Centre for Research and Innovation in Science Education, Miranda House, and Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India. Electronic address: etisaraav@gmail.com.
authors.forename: Iti
authors.initials: I
authors.lastname: Saraav
authors.affiliation: D S Kothari Centre for Research and Innovation in Science Education, Miranda House, and Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India. Electronic address: kirti.pandey5@gmail.com.
authors.forename: Kirti
authors.initials: K
authors.lastname: Pandey
authors.affiliation: D S Kothari Centre for Research and Innovation in Science Education, Miranda House, and Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India. Electronic address: monikasharma.mh@gmail.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: D S Kothari Centre for Research and Innovation in Science Education, Miranda House, and Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India. Electronic address: singhswati.mh@gmail.com.
authors.forename: Swati
authors.initials: S
authors.lastname: Singh
authors.affiliation: Open Source Drug Discovery Unit, Council of Scientific and Industrial Research (CSIR), Delhi 110001, India. Electronic address: prasundutta87@gmail.com.
authors.forename: Prasun
authors.initials: P
authors.lastname: Dutta
authors.affiliation: Open Source Drug Discovery Unit, Council of Scientific and Industrial Research (CSIR), Delhi 110001, India. Electronic address: anshu@csir.res.in.
authors.forename: Anshu
authors.initials: A
authors.lastname: Bhardwaj
authors.affiliation: D S Kothari Centre for Research and Innovation in Science Education, Miranda House, and Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India. Electronic address: sadhna.sharma@mirandahouse.ac.in.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D000071497:Immunogenicity, Vaccine; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D037521:Virulence Factors; D002265:Carboxylic Ester Hydrolases; C000594149:LipY protein, Mycobacterium tuberculosis
keywords: Antigenic T-cell epitopes; Mycobacterium tuberculosis; Tuberculosis; Vaccine candidates; mymA operon