Facilitated antigen uptake and timed exposure to TLR ligands dictate the antigen-presenting potential of plasmacytoid DCs

Journal of Leukocyte Biology

Kris Thielemans¹  Bart N. Lambrecht, ³  Fillipe Branco Madeira²  Mirjam Kool, ³  Menno van Nimwegen⁴  Hamida Hammad  and²  Henk C. Hoogsteden⁴  Femke Muskens⁴  Harmjan Kuipers⁴  Corine GeurtsVanKessel⁴ 

[1] Department of Physiology, Free University Brussels, Brussels, Belgium Virology, ErasmusMC, Rotterdam, the Netherlands; Laboratory of Immunoregulation and Mucosal Immunology, University Hospital Ghent, Ghent, Belgium;Departments of Pulmonary Medicine and  Laboratory of Immunoregulation and Mucosal Immunology, University Hospital Ghent, Ghent, Belgium;Departments of Pulmonary Medicine and Virology, ErasmusMC, Rotterdam, the Netherlands;

关键词: dentritic cells;    antigen processing;    influenza;    OVA;   

DOI  :  10.1189/jlb.0610342

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Subsets of antigen-presenting cDCs have a differential capacity to present exogenous and endogenous protein antigens to CD4+ and/or CD8+ T lymphocytes, depending on expression of antigen-uptake receptors, processing machinery, and microbial instruction. pDCs are also capable of antigen presentation, but the conditions under which they do this have not been systematically addressed. Highly purified cDCs and pDCs were exposed to exogenous, soluble OVA peptide or whole protein. Alternatively, they were made to express cytoplasmic or endosomal OVA by retroviral transduction or by infection with influenza virus containing OVA epitopes. Like cDCs, pDCs expressed the MHC I processing machinery and could present endogenous or cross-present exogenous OVA to CD8+ T cells, provided they had been stimulated by CpG motif TLR9 ligands or by influenza. Unlike cDCs, the cross-priming activity of pDCs was enhanced, not decreased, by simultaneous TLR stimulation. Processing and presentation of exogenous OVA to CD4+ T cells required TLR9 ligation prior to antigen encounter and addition of OVA-specific Igs. These stimuli up-regulated critical MHC II processing machinery and enhanced routing to acidic endosomal organelles in a FcγRII-dependent manner. Endogenous antigen was not presented to CD4+ T cells when expressed in the cytoplasm of pDCs by retrovirus or contained in influenza, unless an Ii-chain-derived endosomal routing signal was present. Thus, timing of TLR ligation and facilitated antigen uptake dictate the potential of pDCs to present endogenous or exogenous antigen by influencing endosomal traffic and antigen-processing machinery.

【 授权许可】

Unknown