Marginal zone B cells acquire dendritic cell functions by trogocytosis.

Marginal zone (MZ) B cells produce broad-spectrum antibodies that protect against infection early in life. In some instances, antibody production requires MZ B cells to display pathogen antigens bound to major histocompatibility complex class II (MHC II) molecules to T cells. We describe the trogocytic acquisition of these molecules from conventional dendritic cells (cDCs).

Endogenous Murine BST-2/Tetherin Is Not a Major Restriction Factor of Influenza A Virus Infection.

BST-2 (tetherin, CD317, HM1.24) restricts virus growth by tethering enveloped viruses to the cell surface. The role of BST-2 during influenza A virus infection (IAV) is controversial.

Inosine-mediated modulation of RNA sensing by Toll-like receptor 7 (TLR7) and TLR8.

RNA-specific adenosine deaminase (ADAR)-mediated adenosine-to-inosine (A-to-I) editing is a critical arm of the antiviral response. However, mechanistic insights into how A-to-I RNA editing affects viral infection are lacking. We posited that inosine incorporation into RNA facilitates sensing of nonself RNA by innate immune sensors and accordingly investigated the impact of inosine-modified RNA on Toll-like receptor 7 and 8 (TLR7/8) sensing.

Hepatitis B virus-like particles access major histocompatibility class I and II antigen presentation pathways in primary dendritic cells.

Virus-like particles (VLPs) represent high density displays of viral proteins that efficiently trigger immunity. VLPs composed of the small hepatitis B virus envelope protein (HBsAgS) are useful vaccine platforms that induce humoral and cellular immune responses. Notably, however, some studies suggest HBsAgS VLPs impair dendritic cell (DC) function.

Targeting antigen to bone marrow stromal cell-2 expressed by conventional and plasmacytoid dendritic cells elicits efficient antigen presentation.

Bone marrow stromal cell-2 (BST-2) has major roles in viral tethering and modulation of interferon production. Here we investigate BST-2 as a receptor for the delivery of antigen to dendritic cells (DCs). We show that BST-2 is expressed by a panel of mouse and human DC subsets, particularly under inflammatory conditions.

Control of MHC II antigen presentation by ubiquitination.

MHC II antigen presentation is a critical pathway involved in the activation of the adaptive immune system. Tight regulatory controls are necessary to ensure appropriate MHC II antigen presentation. One mechanism for regulating this pathway is ubiquitination.

Influenza epitope-specific CD8+ T cell avidity, but not cytokine polyfunctionality, can be determined by TCRβ clonotype.

Cytokine polyfunctionality has recently emerged as a correlate of effective CTL immunity to viruses and tumors. Although the determinants of polyfunctionality remain unclear, there are published instances of a link between the production of multiple effector molecules and the peptide plus MHC class I molecule avidity of T cell populations. Influenza A virus infection of C57BL/6J mice induces CTL populations specific for multiple viral epitopes, each with varying proportions of monofunctional (IFN-γ(+) only) or polyfunctional (IFN-γ(+)TNF-α(+)IL-2(+)) CTLs.

Narrowed TCR diversity for immunised mice challenged with recombinant influenza A-HIV Env(311-320) virus.

Understanding CD8+ T cell responses generated by live virus vectors is critical for the rational design of next generation HIV CTL-based vaccines. We used recombinant influenza viruses expressing the HIV Env(311-320) peptide in the neuraminidase stalk to study response magnitude, cytokine production and repertoire diversity for the elicited CD8+ D(d)Env(311) CTL set. The insertion of the CD8+ D(d)Env(311) epitope into the NA stalk resulted in a decrease in viral fitness that was reflected in lower lung viral titres.

Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic.

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection.

CTL mediate anti-viral immunity via targeted exocytosis of cytolytic granules containing perforin and members of the granzyme (grz) serine protease family. Here, we provide the first analysis of grzA protein expression by murine anti-viral CTL. During the progression of influenza A virus infection, CTL expressed two divergent cytolytic phenotypes: grzA(-)B(+) and grzA(+)B(+).

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection.

Antigen expressed as MHC Class I glycoprotein (pMHCI) complexes on dendritic cells is the primary driver of CD8(+) T cell clonal expansion and differentiation. As we seek to define the molecular differences between acutely stimulated cytotoxic T lymphocyte (CTL) effectors and long-lived memory T cells, it is essential that we understand the duration of in vivo pMHCI persistence. Although infectious influenza A virus is readily cleared by mammalian hosts, that does not necessarily mean that all influenza antigen is totally eliminated.