Premium
Conserved mycobacterial lipoglycoproteins activate TLR2 but also require glycosylation for antigen presentation to T cells
Author(s) -
Fabri Mario,
Sieling Peter A,
Hill Preston J,
Dobos Karen M,
Brookman Kerry,
Kuhlman Andrew M,
Krutzik Stephan R,
Rea Thomas H,
Heaslip Darragh G,
Belisle John T,
Modlin Robert L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.421
Subject(s) - antigen , antigen presentation , mycobacterium kansasii , antigen presenting cell , glycosylation , recombinant dna , biology , t cell , microbiology and biotechnology , mycobacterium , immunology , bacteria , biochemistry , immune system , gene , genetics
CD4+ T cell clones derived from a leprosy lesion and patient blood were used to monitor the isolation and identification of an antigen associated with the self‐limited form of the disease. Biochemical purification and genetic analysis identified the T cell antigen as a conserved mycobacterial lipoglycoprotein LprG. Antigen presentation of LprG to CD4+ T cells required specific MHC class II restriction molecules and intracellular processing. Although LprG activated TLR2, this alone was not sufficient to stimulate nor did it inhibit antigen presentation. A striking finding was that the carbohydrate moieties of LprG were required for optimal presentation to T cells, since recombinant LprG produced in Escherichia coli , or recombinant LprG produced in Mycobacterium smegmatis and digested by α‐mannosidase were not recognized by T cells. This study demonstrates that the universe of bacterial T cell antigens includes lipoglycoproteins, which act as TLR2 ligands but also require glycosylation for antigen presentation in vivo. This work was supported in part by grants from the National Institutes of Health (AI22553, AI47868) to RLM, Deutsche Forschungsgemeinschaft(FA849/1‐1) to MF, and material support through NIH contracts N01 AI75320 (JTB)