Inhibition of CD1d1‐mediated antigen presentation by the vaccinia virus B1R and H5R molecules

Abstract

Vaccinia virus (VV) has been most commonly used as the vaccine to protect individuals against the causative agent of smallpox (variola virus), but it also uses a number of strategies meant to evade or blunt the host's antiviral immune response. Natural killer T (NKT) cells are a subset of immunoregulatory CD1d‐restricted T lymphocytes believed to bridge the innate and adaptive immune responses. It is shown here that the VV‐encoded molecules, B1R and H5R, play a role in the ability of VV to inhibit CD1d‐mediated antigen presentation to NKT cells. These are the first poxvirus‐encoded molecules identified that can play such a role in the evasion of an important component of the innate immune response.

Dietary fatty acids modulate antigen presentation to hepatic NKT cells in nonalcoholic fatty liver disease

“…V ␣ 14 + mouse CD1d-specifi c NKT hybridoma cells (DN32.D3) were cocultured with a mouse fi broblast cell line (LCD1dwt) that has been stably transfected with CD1d and naturally expresses an endogenous NKT cell ligand ( 18 ), in the presence or absence of FFAs, such as palmitoleic acid (PA), oleic acid (OA), and docosahexaenoic acid (DHA) (Sigma-Aldrich, St Louis, MO). IL-2 released from NKT cells to the media were determined by commercially available, mouse-compatible ELISAs (R and D systems, Inc., Minneapolis, MN) with recombinant murine cytokines as standards.…”

NKT cells: Friend or foe during viral infections?

“…This effect depends on a tyrosine-based motif present in the CD1d intracytoplasmic tail that interacts with the viral Nef protein [8,9]. In contrast, vaccinia virus and vesicular stomatitis virus (VSV) inhibit CD1d-mediated antigen presentation (in mice) by altering the intracellular trafficking of CD1d without reducing its cell surface expression [10,11]. Two vaccinia virus proteins (B1R and H5R) and the VSV matrix protein play a role in the inhibition of CD1d-mediated antigen presentation by modulating mitogenactivated protein kinase signaling.…”

Invariant NKT cells reduce the immunosuppressive activity of influenza A virus–induced myeloid-derived suppressor cells in mice and humans

“…In CD1d-deficient BALB/c mice, numbers of respiratory syncytial virus-specific (RSV-specific) CD8 + MHC class Irestricted T cells were reduced, suggesting that CD1d-restricted T cells influence the adaptive immune response to RSV infection (32). The activity of iNKT cells against viral infections is further confirmed by the presence of viral mechanisms capable of downregulating CD1d molecules (33)(34)(35). However, it remains unclear whether iNKT cells can facilitate IAV-specific immune responses, contributing to survival of IAV-infected mice.…”