A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans

Simple item page
dc.contributor.authorArlehamn, Cecilia S Lindestamen_ZA
dc.contributor.authorMcKinney, Denise Men_ZA
dc.contributor.authorCarpenter, Chelseaen_ZA
dc.contributor.authorPaul, Sinuen_ZA
dc.contributor.authorRozot, Virginieen_ZA
dc.contributor.authorMakgotlho, Edwarden_ZA
dc.contributor.authorGregg, Yolandeen_ZA
dc.contributor.authorVan Rooyen, Micheleen_ZA
dc.contributor.authorErnst, Joel Den_ZA
dc.contributor.authorHatherill, Marken_ZA
dc.contributor.authorHanekom, Willem Aen_ZA
dc.contributor.authorPeters, Bjoernen_ZA
dc.contributor.authorScriba, Thomas Jen_ZA
dc.contributor.authorSette, Alessandroen_ZA
dc.date.accessioned2016-10-31T07:36:21Z
dc.date.available2016-10-31T07:36:21Z
dc.date.issued2016en_ZA
dc.description.abstractAuthor Summary: Human pathogen-specific immune responses are tremendously complex and the techniques to study them ever expanding. There is an urgent need for a quantitative analysis and better understanding of pathogen-specific immune responses. Mycobacterium tuberculosis (Mtb) is one of the leading causes of mortality due to an infectious agent worldwide. Here, we were able to quantify the Mtb-specific response in healthy individuals with Mtb infection from South Africa. The response is highly diverse and 66 epitopes are required to capture 80% of the total reactivity. Our study also show that the majority of the identified epitopes are restricted by multiple HLA alleles. Thus, technical advances are required to capture and characterize the complete pathogen-specific response. This study demonstrates further that the approach combining identified epitopes into "megapools" allows capturing a large fraction of the total reactivity. This suggests that this technique is generally applicable to the characterization of immunity to other complex pathogens. Together, our data provide for the first time a quantitative analysis of the complex pathogen-specific T cell response and provide a new understanding of human infections in a natural infection setting.en_ZA
dc.identifier.apacitationArlehamn, C. S. L., McKinney, D. M., Carpenter, C., Paul, S., Rozot, V., Makgotlho, E., ... Sette, A. (2016). A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans. <i>PLoS One</i>, http://hdl.handle.net/11427/22346en_ZA
dc.identifier.chicagocitationArlehamn, Cecilia S Lindestam, Denise M McKinney, Chelsea Carpenter, Sinu Paul, Virginie Rozot, Edward Makgotlho, Yolande Gregg, et al "A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans." <i>PLoS One</i> (2016) http://hdl.handle.net/11427/22346en_ZA
dc.identifier.citationArlehamn, C. S. L., McKinney, D. M., Carpenter, C., Paul, S., Rozot, V., Makgotlho, E., ... & Hanekom, W. A. (2016). A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans. PLoS Pathog, 12(7), e1005760. doi:10.1371/journal.ppat.1005760en_ZA
dc.identifier.ris TY - Journal Article AU - Arlehamn, Cecilia S Lindestam AU - McKinney, Denise M AU - Carpenter, Chelsea AU - Paul, Sinu AU - Rozot, Virginie AU - Makgotlho, Edward AU - Gregg, Yolande AU - Van Rooyen, Michele AU - Ernst, Joel D AU - Hatherill, Mark AU - Hanekom, Willem A AU - Peters, Bjoern AU - Scriba, Thomas J AU - Sette, Alessandro AB - Author Summary: Human pathogen-specific immune responses are tremendously complex and the techniques to study them ever expanding. There is an urgent need for a quantitative analysis and better understanding of pathogen-specific immune responses. Mycobacterium tuberculosis (Mtb) is one of the leading causes of mortality due to an infectious agent worldwide. Here, we were able to quantify the Mtb-specific response in healthy individuals with Mtb infection from South Africa. The response is highly diverse and 66 epitopes are required to capture 80% of the total reactivity. Our study also show that the majority of the identified epitopes are restricted by multiple HLA alleles. Thus, technical advances are required to capture and characterize the complete pathogen-specific response. This study demonstrates further that the approach combining identified epitopes into "megapools" allows capturing a large fraction of the total reactivity. This suggests that this technique is generally applicable to the characterization of immunity to other complex pathogens. Together, our data provide for the first time a quantitative analysis of the complex pathogen-specific T cell response and provide a new understanding of human infections in a natural infection setting. DA - 2016 DB - OpenUCT DO - 10.1371/journal.ppat.1005760 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans TI - A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans UR - http://hdl.handle.net/11427/22346 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1005760en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22346
dc.identifier.vancouvercitationArlehamn CSL, McKinney DM, Carpenter C, Paul S, Rozot V, Makgotlho E, et al. A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans. PLoS One. 2016; http://hdl.handle.net/11427/22346.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentSouth African Tuberculosis Vaccine Initiative (SATVI)en_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2016 Lindestam Arlehamn et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherT helper cellsen_ZA
dc.subject.otherVaccinesen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherAntigensen_ZA
dc.subject.otherImmune responseen_ZA
dc.titleA quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africansen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Arlehamn_Quantitative_Analysis_Complexity_2016.pdf
Size:
2.01 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles