adaptive evolution of the chlamydia trachomatis dominant antigen reveals distinct evolutionary scenarios for b- and t-cell epitopes worldwide survey自适应进化的沙眼衣原体主要抗原显示不同的进化场景b和t细胞抗原表位的世界范围的调查.pdfVIP

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adaptive evolution of the chlamydia trachomatis dominant antigen reveals distinct evolutionary scenarios for b- and t-cell epitopes worldwide survey自适应进化的沙眼衣原体主要抗原显示不同的进化场景b和t细胞抗原表位的世界范围的调查.pdf

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adaptive evolution of the chlamydia trachomatis dominant antigen reveals distinct evolutionary scenarios for b- and t-cell epitopes worldwide survey自适应进化的沙眼衣原体主要抗原显示不同的进化场景b和t细胞抗原表位的世界范围的调查

Adaptive Evolution of the Chlamydia trachomatis Dominant Antigen Reveals Distinct Evolutionary Scenarios for B- and T-cell Epitopes: Worldwide Survey 1 2 1 ˜ 1 Alexandra Nunes , Paulo J. Nogueira , Maria J. Borrego , Joao P. Gomes * 1 Department of Infectious Diseases, National Institute of Health, Lisbon, Portugal, 2 Department of Epidemiology, National Institute of Health, Lisbon, Portugal Abstract Background: Chlamydia trachomatis is one of the most disseminated human pathogens, for which no vaccine is available yet. Understanding the impact of the host pressure on pathogen antigens is crucial, but so far it was only assessed for highly-restricted geographic areas. We aimed to evaluate the evolutionary picture of the chlamydial key antigen (MOMP), which is one of the leading multi-subunit vaccine candidates, in a worldwide basis. Methodology/Principal Findings: Using genetics, molecular evolution methods and mathematical modelling, we analyzed all MOMP sequences reported worldwide, composed by 5026 strains from 33 geographic regions of five continents. Overall, 35.9% of variants were detected. The evolutionary pattern of MOMP amino acid gains/losses was found to differ from the remaining chromosome, reflecting the demanding constraints of this porin, adhesin and dominant antigen. Amino acid changes were 4.3-fold more frequent in host-interacting domains (P,10212), specifically within B-cell epitopes (P,1025), where 25% of them are at fixation (P,1025). According to the typical pathogen-host arms race, this rampant B-cell antigenic variation likely represents neutralization escape mutants, as some mutations were previously shown to abrogate neutralization of chlamydial infectivity in vitro. In contrast, T-cell clusters