Potentiating vaccine immunogenicity by manipulating the HVEM/BTLA pathway and other co-stimulatory and co-inhibitory signals of the immune system

Abstract

Adaptive immune responses are tightly controlled by activating and inhibitory signals, which ensure an effective defense against pathogens while preventing detrimental reactions. Regulation is provided through sets of receptors and ligands expressed on lymphocytes and antigen-presenting cells. Expression of the regulatory molecules is up- or downregulated during immune responses and some pathways provide positive or negative signals depending on the state of differentiation of the cells. Many of the ligands and receptors can engage multiple binding partners and thus have distinct effects on down-stream signaling. Medicinal manipulations of such pathways are being explored to augment antigen-driven immune responses through activation of positive or blockade of negative signals. In this review we provide a brief description of the co-stimulatory and co-inhibitory receptors and ligands with focus on the pathways mediated by the herpes virus entry mediator (HVEM) and the B and T lymphocyte mediator (BTLA).