Complement opsonization of HIV-1 results in a different intracellular processing pattern and enhanced MHC class I presentation by dendritic cells.

Veronica Tjomsland,Garrett Westmacott,Karlhans F Che,Rada Ellegård,Jeffrey D Lifson,Marie Larsson,Adam Burgener,Kenzie Mogk,Jorma Hinkula

doi:10.1002/eji.201242935

Abstract

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.

Highlights

The most frequent port of entry for HIV-1 is the genital mucosa and in these tissues, DCs can be one of the first cell types that encounter the virus
Taking into consideration our previous findings that mannan decreased the amount of virions internalized in immature DCs (IDCs) by 48% for free HIV-1 (F-HIV) and 45% for complement opsonized HIV-1BaL (C-HIV) [12], these results indicate that C-type lectins trafficked HIV-1 away from the pathway leading to MHC class II (MHCII) presentation and promoted MHC class I (MHCI) presentation by IDCs
Our present study evaluated the impact of opsonization of HIV-1 on processing and antigen presentation

Summary

Introduction

The most frequent port of entry for HIV-1 is the genital mucosa and in these tissues, DCs can be one of the first cell types that encounter the virus. The majority of HIV-1 virions captured by DCs are internalized into endosomal compartments and can either be processed for MHC class II (MHCII) presentation or enter into the cytosol via CD4/coreceptor for MHC class I (MHCI) presentation [5,6]. Virions are processed by proteases and the viral antigens can be loaded onto MHCII molecules, or degraded in the lysosomal compartments [7]. A small fraction of endocytosed virions can remain infectious for days in nonacidic intracellular compartments existing in mature DCs (MDCs), but not in immature DCs (IDCs) [8] suggesting differences in trafficking and processing pathways between IDCs and MDCs [8]

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