Complement opsonization of HIV-1 results in a different intracellular processing pattern and enhanced MHC class I presentation by dendritic cells
2013 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 43, no 6, 1470-1483 p.Article in journal (Refereed) Published
Induction of optimal HIV-1-specific T-cell responses, which can contribute to controlling viral infection in vivo, depends on antigen processing and presentation processes occurring in DCs. Opsonization can influence the routing of antigen processing and pathways used for presentation. We studied antigen proteolysis and the role of endocytic receptors in MHC class I (MHCI) and II (MHCII) presentation of antigens derived from HIV-1 in human monocyte-derived immature DCs (IDCs) and mature DCs, comparing free and complement opsonized HIV-1 particles. Opsonization of virions promoted MHCI presentation by DCs, indicating that complement opsonization routes more virions toward the MHCI presentation pathway. Blockade of macrophage mannose receptor (MMR) and β7-integrin enhanced MHCI and MHCII presentation by IDCs and mature DCs, whereas the block of complement receptor 3 decreased MHCI and MHCII presentation. In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure; complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and β7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery.
Place, publisher, year, edition, pages
Wiley-VCH Verlag , 2013. Vol. 43, no 6, 1470-1483 p.
Antigen presentation, Antigen processing, Complement opsonization, Dendritic cells, HIV-1
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-95970DOI: 10.1002/eji.201242935ISI: 000320785700015OAI: oai:DiVA.org:liu-95970DiVA: diva2:641640
Funding Agencies|Swedish Research Council||Swedish, Physicians against AIDS research Foundation||Swedish International Development Cooperation Agency||SIDA SARC||VINNMER for Vinnova||Linkoping University Hospital Research Fund||C ALF||Swedish Society of Medicine||National Cancer Institute, National Institutes of Health|HHSN261200800001E||AI52731|2013-08-192013-08-122013-09-19