title: Analysis of the DosR regulon genes to select cytotoxic T lymphocyte epitope specific vaccine candidates using a reverse vaccinology approach.
abstract: OBJECTIVE
  There is an urgent need for a more effective vaccine against Mycobacterium tuberculosis (Mtb). Although CD4+ T cells play a central role in host immunity to Mtb, recent evidence suggests a critical role of CD8+ T cells in combating Mtb. In the present study, we have predicted HLA antigen class I binding peptides of DosR operon using an in-silico approach. This method is useful as an initial computational filtration of probable epitopes based on their binding ability and antigenicity.
  
  
  METHODS
  CD8+ epitopes were predicted by software NetMHC 3.4 and BIMAS. Self-peptides were found and excluded by indigenously developed Perl script. Antigenicity of promiscuous peptides was predicted using a VaxiJen server. The top VaxiJen scoring antigenic peptides were docked to globally relevant HLA allele using CABS dock and Hex program.
  
  
  RESULTS
  A total of 1436 overlapping nonamer peptides were generated which gave 46 promiscuous epitopes, 25 were predicted to be antigenic. Rv2627 epitope "SAFRPPLV" which gave the highest Vaxijen score of 1.9157 and showed binding to all the three HLA loci. The top VaxiJen scoring antigenic peptides were docked and had significant interactions with residues of the HLA class I molecule indicating them to be good cytotoxic T lymphocyte epitopes.
  
  
  CONCLUSIONS
  Our study has generated several promiscuous antigenic peptides capable of binding to major histocompatibility complex class I with high affinity. These epitopes can become part of a postexposure multivalent subunit vaccine upon experimental validation.
authors.affiliation: DS Kothari Center for Research and Innovation in Science Education, Miranda House, University of Delhi, Delhi, India; Department of Zoology, Miranda House, University of Delhi, Delhi, India.
authors.forename: Kirti
authors.initials: K
authors.lastname: Pandey
authors.affiliation: DS Kothari Center for Research and Innovation in Science Education, Miranda House, University of Delhi, Delhi, India; Department of Zoology, Miranda House, University of Delhi, Delhi, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: DS Kothari Center for Research and Innovation in Science Education, Miranda House, University of Delhi, Delhi, India; Department of Zoology, Miranda House, University of Delhi, Delhi, India.
authors.forename: Iti
authors.initials: I
authors.lastname: Saarav
authors.affiliation: DS Kothari Center for Research and Innovation in Science Education, Miranda House, University of Delhi, Delhi, India; Department of Zoology, Miranda House, University of Delhi, Delhi, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Singh
authors.affiliation: Open Source Drug Discovery Unit, Council of Scientific and Industrial Research, Delhi, India.
authors.forename: Prasun
authors.initials: P
authors.lastname: Dutta
authors.affiliation: Open Source Drug Discovery Unit, Council of Scientific and Industrial Research, Delhi, India.
authors.forename: Anshu
authors.initials: A
authors.lastname: Bhardwaj
authors.affiliation: DS Kothari Center for Research and Innovation in Science Education, Miranda House, University of Delhi, Delhi, India; Department of Zoology, Miranda House, University of Delhi, Delhi, India. Electronic address: sadhna.sharma@mirandahouse.ac.in.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003198:Computer Simulation; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics* / Q000276:immunology*; D018085:Regulon; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D032581:Tuberculosis Vaccines; D011494:Protein Kinases
keywords: CD8+ T cell epitopes; Cellular immunity; DosR operon; Mycobacterium tuberculosis; TB vaccines