Influenza A virus (IAV) strains are denoted by the subtype of their hemagglutinin (HA) and neuraminidase (NA) virion surface proteins. Major changes in HA subtype among strains circulating in humans are referred to as "antigenic shift". Antigenic shift can occur by two means; direct transmission of a zoonotic strain to humans or through reshuffling of the segmented genome in cells co-infected with animal and human strains. The lack of circulating anti-HA antibodies in human populations to a novel IAV results in extremely high frequency of illness and the potential for severe morbidity and mortality on a world-wide basis; the dreaded pandemic. Such pandemics could be partially controlled by developing a vaccine that generates effective heterosubtypic immunity (HSI) based on immune recognition of IAV antigens conserved across all viral strains. While it has long been known that T cells exhibit such broad cross-reactive specificity that could provide effective HSI, recent animal studies suggest a potential role for antibodies as well. Here we review current knowledge of the mechanisms contributing to HSI to influenza and speculate on the potential for this approach to contribute to public health.

Upon productive interaction of CD4 T cells with antigen-presenting cells (APCs),

Proteasomes are multisubunit proteases that initiate degradation of many Ags presented by MHC class I molecules. Vertebrates express alternate forms of each of the three catalytic proteasome subunits: standard subunits, and immunosubunits, which are constitutively expressed by APCs and are induced in other cell types by exposure to cytokines. The assembly of mixed proteasomes containing standard subunits and immunosubunits is regulated in a tissue specific manner. In this study, we report that the presence of mixed proteasomes in immune cells in LMP2−/− mice compromises multiple components that contribute to the generation of antiviral Ab responses, including splenic B cell numbers, survival and function of adoptively transferred B cells, Th cell function, and dendritic cell secretion of IL-6, TNF-α, IL-1β, and type I IFNs. These defects did not result from compromised overall protein degradation, rather they were associated with altered NF-κB activity. These findings demonstrate an important role for immunoproteasomes in immune cell function beyond their contribution to Ag processing.