학술논문
Rare Variable M. tuberculosis Antigens induce predominant Th17 responses in human infection.
Document Type
Author
Ogongo P; Division of Experimental Medicine, University of California, San Francisco, CA, USA.; Department of Tropical and Infectious Diseases, Institute of Primate Research, Nairobi, Kenya.; Wassie L; Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia.; Tran A; Division of Experimental Medicine, University of California, San Francisco, CA, USA.; Columbus D; Division of Experimental Medicine, University of California, San Francisco, CA, USA.; Sharling L; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Ouma G; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.; Ouma SG; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.; Bobosha K; Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia.; Lindestam Arlehamn CS; Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, USA.; Gandhi NR; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.; Department of Global Health, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Auld SC; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Department of Global Health, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Rengarajan J; Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Day CL; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.; Altman JD; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Blumberg HM; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.; Department of Global Health, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Ernst JD; Division of Experimental Medicine, University of California, San Francisco, CA, USA.
Source
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
CD4 T cells are essential for immunity to M. tuberculosis ( Mtb ), and emerging evidence indicates that IL-17-producing Th17 cells contribute to immunity to Mtb . While identifying protective T cell effector functions is important for TB vaccine design, T cell antigen specificity is also likely to be important. To identify antigens that induce protective immunity, we reasoned that as in other pathogens, effective immune recognition drives sequence diversity in individual Mtb antigens. We previously identified Mtb genes under evolutionary diversifying selection pressure whose products we term Rare Variable Mtb Antigens (RVMA). Here, in two distinct human cohorts with recent exposure to TB, we found that RVMA preferentially induce CD4 T cells that express RoRγt and produce IL-17, in contrast to 'classical' Mtb antigens that induce T cells that produce IFNγ. Our results suggest that RVMA can be valuable antigens in vaccines for those already infected with Mtb to amplify existing antigen-specific Th17 responses to prevent TB disease.