Equivalent T cell epitope promiscuity in ecologically diverse human pathogens.
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.
Department of Pathology, New York University School of Medicine, New York, New York, USA.
Kirsten E
KE
Wiens
Harish
H
Swaminathan
Richard
R
Copin
Desmond S
DS
Lun
Joel D
JD
Ernst
D000483:Alleles; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001408:Bacillus anthracis / Q000235:genetics / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D003017:Clostridium tetani / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D014644:Genetic Variation / Q000276:immunology*; D006678:HIV / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D013744:Tetanus Toxin; C030325:anthrax toxin