Circulating antigen presenting cells in chronically infected HBV patients do not constitutively cross-present HBV antigens (105.22)

Abstract

Abstract Persistent exposure to antigen is thought to play a primary role in dysfunction of virus-specific T cells in chronic infection. Our study sought to determine whether antigen presenting cells (APCs) in the blood of chronic HBV patients constitutively cross-present circulating HBV antigen to virus-specific CD8 T cells. We isolated dendritic cells, CD14 or CD16 monocytes and B cells from HLA-A2+ healthy donors and chronic HBV patients with 10^8 IU HBV DNA/ml serum. APCs were co-incubated with TCR-redirected T cells specific for HLA-A2 restricted HBc18-27 and HBs183-91 epitopes and activation was monitored by staining for IFN-γ. APCs were also stained with TCR-like antibodies specific for the same peptide/HLA-A2 complexes. We did not observe any HBc18-27- or HBs183-91-specific T cell activation following incubation with sorted healthy donor APCs. Nor did we see T cell activation after co-culture with APCs isolated from chronic HBV patient PBMCs. Staining with TCR-like antibodies confirmed that there were no detectable HBc18-27- or HBs183-91-HLA-A2 complexes constitutively present on the cell surface. IFN-γ production and TCR-like antibody staining was observed with peptide loaded APCs. Our data suggests that APCs in the peripheral blood of chronically infected patients do not constitutively cross-present antigen to virus-specific CD8 T cells and therefore may not contribute to T cell dysfunction.