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dc.contributor.authorLi, Yuan
dc.contributor.authorGierahn, Todd
dc.contributor.authorThompson, Claudette M.
dc.contributor.authorTrzciński, Krzysztof
dc.contributor.authorFord, Christopher Burton
dc.contributor.authorCroucher, Nicholas Jason
dc.contributor.authorGouveia, Paulo
dc.contributor.authorFlechtner, Jessica B.
dc.contributor.authorMalley, Richard
dc.contributor.authorLipsitch, Marc
dc.date.accessioned2013-04-22T17:39:00Z
dc.date.issued2012
dc.identifier.citationLi, Yuan, Todd Gierahn, Claudette M. Thompson, Krzysztof Trzciński, Christopher B. Ford, Nicholas Croucher, Paulo Gouveia, Jessica B. Flechtner, Richard Malley, and Marc Lipsitch. 2012. Distinct effects on diversifying selection by two mechanisms of immunity against Streptococcus pneumoniae. PLoS Pathogens 8(11): e1002989.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.issn1553-7374en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10579212
dc.description.abstractAntigenic variation to evade host immunity has long been assumed to be a driving force of diversifying selection in pathogens. Colonization by Streptococcus pneumoniae, which is central to the organism's transmission and therefore evolution, is limited by two arms of the immune system: antibody- and T cell- mediated immunity. In particular, the effector activity of CD4+ TH17 cell mediated immunity has been shown to act in trans, clearing co-colonizing pneumococci that do not bear the relevant antigen. It is thus unclear whether TH17 cell immunity allows benefit of antigenic variation and contributes to diversifying selection. Here we show that antigen-specific CD4+ TH17 cell immunity almost equally reduces colonization by both an antigen-positive strain and a co-colonized, antigen-negative strain in a mouse model of pneumococcal carriage, thus potentially minimizing the advantage of escape from this type of immunity. Using a proteomic screening approach, we identified a list of candidate human CD4+ TH17 cell antigens. Using this list and a previously published list of pneumococcal Antibody antigens, we bioinformatically assessed the signals of diversifying selection among the identified antigens compared to non-antigens. We found that Antibody antigen genes were significantly more likely to be under diversifying selection than the TH17 cell antigen genes, which were indistinguishable from non-antigens. Within the Antibody antigens, epitopes recognized by human antibodies showed stronger evidence of diversifying selection. Taken together, the data suggest that TH17 cell-mediated immunity, one form of T cell immunity that is important to limit carriage of antigen-positive pneumococcus, favors little diversifying selection in the targeted antigen. The results could provide new insight into pneumococcal vaccine design.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.1002989en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493470/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectEvolutionary Biologyen_US
dc.subjectComparative Genomicsen_US
dc.subjectEvolutionary Immunologyen_US
dc.subjectEvolutionary Processesen_US
dc.subjectGenomic Evolutionen_US
dc.subjectImmunologyen_US
dc.subjectGenetics of the Immune Systemen_US
dc.subjectImmune Responseen_US
dc.subjectImmunityen_US
dc.titleDistinct Effects on Diversifying Selection by Two Mechanisms of Immunity Against Streptococcus pneumoniaeen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorMalley, Richard
dc.date.available2013-04-22T17:39:00Z
dc.identifier.doi10.1371/journal.ppat.1002989*
dash.contributor.affiliatedFord, Christopher Burton
dash.contributor.affiliatedLi, Yuan
dash.contributor.affiliatedThompson, Claudette
dash.contributor.affiliatedMalley, Richard
dash.contributor.affiliatedCroucher, Nicholas J
dash.contributor.affiliatedLipsitch, Marc


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