Figure 4.

Distinct antigen presentation pathways regulate the activation of CD1d-restricted T cells. (A) At steady state, endogenous lipids are loaded onto CD1d in the endoplasmic reticulum (ER) compartment with the help of microsomal triglyceride transfer protein (MTP) and directly activate type II NKT cells. Activation of type I NKT cells requires CD1d endocytosis and replacement of the bound lipids by antigens present in the endosomal compartment, a process that is edited by saposins. (B) Inflammation and viral infection lead to alterations of the endogenous lipid synthesis and increased expression of secretory phospholipase (sPLA₂). This results in endogenous phospholipid hydrolysis and generation of stimulatory lysophospholipids or enhanced synthesis and/or decreased degradation of stimulatory lipids for type I and type II NKT cells, respectively. (C) Pathogenic bacteria, fungi, or parasites express microbial lipids that can be loaded onto CD1d molecules in endosomal compartments, resulting in the activation of type I and II NKT cells. APC, antigen-presenting cell; NKT, natural killer T cell; MTP, microsomal triglyceride transfer protein.