PMID- 23951341
OWN - NLM
STAT- MEDLINE
DCOM- 20140303
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - Equivalent T cell epitope promiscuity in ecologically diverse human pathogens.
PG  - e73124
LID - 10.1371/journal.pone.0073124 [doi]
LID - e73124
AB  - BACKGROUND: The HLA (human leukocyte antigen) molecules that present 
      pathogen-derived epitopes to T cells are highly diverse. Correspondingly, many 
      pathogens such as HIV evolve epitope variants in order to evade immune 
      recognition. In contrast, another persistent human pathogen, Mycobacterium 
      tuberculosis, has highly conserved epitope sequences. This raises the question 
      whether there is also a difference in the ability of these pathogens' epitopes to 
      bind diverse HLA alleles, referred to as an epitope's binding promiscuity. To 
      address this question, we compared the in silico HLA binding promiscuity of T 
      cell epitopes from pathogens with distinct infection strategies and outcomes of 
      human exposure. METHODS: We used computer algorithms to predict the binding 
      affinity of experimentally-verified microbial epitope peptides to diverse HLA-DR, 
      HLA-A and HLA-B alleles. We then analyzed binding promiscuity of epitopes derived 
      from HIV and M. tuberculosis. We also analyzed promiscuity of epitopes from 
      Streptococcus pyogenes, which is known to exhibit epitope diversity, and epitopes 
      of Bacillus anthracis and Clostridium tetani toxins, as these bacteria do not 
      depend on human hosts for their survival or replication, and their toxin antigens 
      are highly immunogenic human vaccines. RESULTS: We found that B. anthracis and C. 
      tetani epitopes were the most promiscuous of the group that we analyzed. However, 
      there was no consistent difference or trend in promiscuity in epitopes contained 
      in HIV, M. tuberculosis, and S. pyogenes. CONCLUSIONS: Our results show that 
      human pathogens with distinct immune evasion strategies and epitope diversities 
      exhibit equivalent levels of T cell epitope promiscuity. These results indicate 
      that differences in epitope promiscuity do not account for the observed 
      differences in epitope variation and conservation.
FAU - Wiens, Kirsten E
AU  - Wiens KE
AD  - Department of Pathology, New York University School of Medicine, New York, New 
      York, USA.
FAU - Swaminathan, Harish
AU  - Swaminathan H
FAU - Copin, Richard
AU  - Copin R
FAU - Lun, Desmond S
AU  - Lun DS
FAU - Ernst, Joel D
AU  - Ernst JD
LA  - eng
GR  - R01 AI090928/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130809
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Tetanus Toxin)
RN  - 0 (anthrax toxin)
SB  - IM
MH  - *Alleles
MH  - Antigens, Bacterial/genetics/immunology
MH  - Bacillus anthracis/genetics/immunology
MH  - Bacterial Toxins/genetics/immunology
MH  - Clostridium tetani/genetics/immunology
MH  - Epitopes, T-Lymphocyte/*genetics/immunology
MH  - Gene Frequency
MH  - Genetic Variation/*immunology
MH  - HIV/genetics/immunology
MH  - HLA-A Antigens/genetics/immunology
MH  - HLA-B Antigens/genetics/immunology
MH  - HLA-DR Antigens/genetics/immunology
MH  - Humans
MH  - Immune Evasion/genetics
MH  - Mycobacterium tuberculosis/genetics/immunology
MH  - Streptococcus pyogenes/genetics/immunology
MH  - T-Lymphocytes/*immunology/microbiology/virology
MH  - Tetanus Toxin/genetics/immunology
PMC - PMC3739752
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/08/21 06:00
MHDA- 2014/03/04 06:00
PMCR- 2013/08/09
CRDT- 2013/08/17 06:00
PHST- 2013/02/13 00:00 [received]
PHST- 2013/07/15 00:00 [accepted]
PHST- 2013/08/17 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/03/04 06:00 [medline]
PHST- 2013/08/09 00:00 [pmc-release]
AID - PONE-D-13-06575 [pii]
AID - 10.1371/journal.pone.0073124 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 9;8(8):e73124. doi: 10.1371/journal.pone.0073124. eCollection 
      2013.