Shared pathway of WDFY4-dependent cross-presentation of immune complexes by cDC1 and cDC2.

Priming CD8+ T cells against tumors or viral pathogens results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). Although monocyte-derived DCs and cDC2s can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to evaluate the role of cDC subsets in presentation of cell-associated and immune complex antigens to CD4+ and CD8+ T cells in vivo.

Type I interferon signaling in dendritic cells limits direct antigen presentation and CD8 T cell responses against an arthritogenic alphavirus.

Ross River virus (RRV) and other alphaviruses cause chronic musculoskeletal syndromes that are associated with viral persistence, which suggests deficits in immune clearance mechanisms, including CD8 T-cell responses. Here, we used a recombinant RRV-gp33 that expresses the immunodominant CD8 T-cell epitope of lymphocytic choriomeningitis virus (LCMV) to directly compare responses with a virus, LCMV, that strongly induces antiviral CD8 T cells. After footpad injection, we detected fewer gp33-specific CD8 T cells in the draining lymph node (DLN) after RRV-gp33 than LCMV infection, despite similar viral RNA levels in the foot.

HIV broadly neutralizing antibody escape dynamics drive the outcome of AAV vectored immunotherapy in humanized mice.

Broadly neutralizing antibodies (bNAbs) have shown promise for prevention and treatment of HIV. Potency and breadth measured are often used as predictors of clinical potential; however, human studies demonstrate that clinical efficacy of bNAbs is undermined by both pre-existing and resistance. Here we find that HIV-infected humanized mice receiving bNAbs delivered via AAV as Vectored ImmunoTherapy (VIT) can be used to identify antibody escape paths, which are largely conserved.