PMID- 26493839
OWN - NLM
STAT- MEDLINE
DCOM- 20160630
LR  - 20181113
IS  - 1471-2172 (Electronic)
IS  - 1471-2172 (Linking)
VI  - 16
DP  - 2015 Oct 22
TI  - Sequence conservation analysis and in silico human leukocyte antigen-peptide 
      binding predictions for the Mtb72F and M72 tuberculosis candidate vaccine 
      antigens.
PG  - 63
LID - 10.1186/s12865-015-0119-7 [doi]
LID - 63
AB  - BACKGROUND: Requisites for an efficacious tuberculosis (TB) vaccine are a minimal 
      genomic diversity among infectious Mycobacterium tuberculosis strains for the 
      selected antigen, and the capability to induce robust T-cell responses in the 
      majority of human populations. A tool in the identification of putative T-cell 
      epitopes is in silico prediction of major histocompatibility complex 
      (MHC)-peptide binding. Candidate TB vaccine antigen Mtb72F and its successor M72 
      are recombinant fusion proteins derived from Mtb32A and Mtb39A (encoded by Rv0125 
      and Rv1196, respectively). Adjuvanted Mtb72F and M72 candidate vaccines were 
      shown to induce CD4(+) T-cell responses in European, US, African and Asian 
      populations. METHODS: Sequence conservation of Mtb32A, Mtb39A, Mtb72F and M72 
      among 46 strains (prevalent Mycobacterium strains causing human TB disease, and 
      H37Ra) was assessed by multiple alignments using ClustalX. For Mtb32A, Mtb39A and 
      Mtb72F, 15-mer human leukocyte antigen (HLA)-class II-binding peptides were 
      predicted for 158 DRB1 alleles prevailing in populations with high TB burden, 6 
      DRB3/4/5, 8 DQ and 6 DP alleles, using NetMHCII-pan-3.0. Results for 3 DRB1 
      alleles were compared with previously published allele-matched in vitro binding 
      data. Additional analyses were done for M72. Nonameric MHC class I-binding 
      peptides in Mtb72F were predicted for three alleles representative of class I 
      supertypes A02, A03 and B07, using seven prediction algorithms. RESULTS: Sequence 
      identity among strains was >/=98 % for each protein. Residue changes in Mtb39A 
      comprised primarily single residue or nucleotide insertions and/or deletions in 
      repeat regions, and were observed in 67 % of strains. For Mtb72F, 156 DRB1, 6 
      DRB3/4/5, 7 DQ and 5 DP alleles were predicted to contain at least one MHC class 
      II-binding peptide, and class I-binding peptides were predicted for each HLA-A/B 
      allele. Comparison of predicted MHC-II-binding peptides with experimental data 
      indicated that the algorithm's sensitivity and specificity were variable among 
      alleles. CONCLUSIONS: The sequences from which Mtb72F and M72 are derived are 
      highly conserved among representative Mycobacterium strains. Predicted putative 
      T-cell epitopes in M72 and/or Mtb72F covered a wide array of HLA alleles. In 
      silico binding predictions for class I- and II-binding putative epitopes can be 
      complemented with biochemical verification of HLA binding capacity, processing 
      and immunogenicity of the predicted peptides.
FAU - Mortier, Marie-Cecile
AU  - Mortier MC
AD  - GSK Vaccines, Rue de l'Institut 89, 1330, Rixensart, Belgium. 
      marie-cecile.mortier@gsk.com.
FAU - Jongert, Erik
AU  - Jongert E
AD  - GSK Vaccines, Rue de l'Institut 89, 1330, Rixensart, Belgium. 
      erik.x.jongert@gsk.com.
FAU - Mettens, Pascal
AU  - Mettens P
AD  - GSK Vaccines, Rue de l'Institut 89, 1330, Rixensart, Belgium. 
      pascal.mettens@gsk.com.
FAU - Ruelle, Jean-Louis
AU  - Ruelle JL
AD  - GSK Vaccines, Rue de l'Institut 89, 1330, Rixensart, Belgium. 
      jean-louis.ruelle@gsk.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151022
PL  - England
TA  - BMC Immunol
JT  - BMC immunology
JID - 100966980
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptides)
RN  - 0 (Tuberculosis Vaccines)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Antigens, Bacterial/*chemistry/*immunology
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - Conserved Sequence
MH  - Epitopes, T-Lymphocyte/*chemistry/*immunology/metabolism
MH  - HLA Antigens/*chemistry/genetics/*immunology/metabolism
MH  - HLA-DRB1 Chains/chemistry/genetics/immunology/metabolism
MH  - Histocompatibility Antigens Class II/chemistry/immunology/metabolism
MH  - Humans
MH  - Mycobacterium/genetics/immunology
MH  - Peptides/chemistry/*immunology
MH  - Protein Binding
MH  - Tuberculosis/immunology/prevention & control
MH  - Tuberculosis Vaccines/*immunology
PMC - PMC4619029
EDAT- 2015/10/27 06:00
MHDA- 2016/07/01 06:00
PMCR- 2015/10/22
CRDT- 2015/10/24 06:00
PHST- 2015/03/09 00:00 [received]
PHST- 2015/09/08 00:00 [accepted]
PHST- 2015/10/24 06:00 [entrez]
PHST- 2015/10/27 06:00 [pubmed]
PHST- 2016/07/01 06:00 [medline]
PHST- 2015/10/22 00:00 [pmc-release]
AID - 10.1186/s12865-015-0119-7 [pii]
AID - 119 [pii]
AID - 10.1186/s12865-015-0119-7 [doi]
PST - epublish
SO  - BMC Immunol. 2015 Oct 22;16:63. doi: 10.1186/s12865-015-0119-7.