CD1 antigen presentation: how it works

Abstract

Key Points

CD1 molecules present foreign and self lipids to diverse T cells and natural killer T (NKT) cells. Whereas the clonally restricted diverse T cells mediate adaptive immunity to microbial lipid antigens, the invariant subset of NKT cells mediates innate immune responses, responding rapidly and en masse.

The classes of lipids presented by CD1 molecules range from self lipids, such as phospholipids and gangliosides, to microbial lipids, such as mycolic acids, polyketides, ceramides, lipopeptides, sulpholipids and diacylglycerols.

CD1 molecules can bind endogenous lipids in the endoplasmic reticulum, where they are assembled. They then follow the secretory pathway to the plasma membrane, before they are internalized. Once internalized, CD1 molecules survey different compartments of the endocytic pathway, load exogenous or different endogenous antigens in these compartments and then return to the plasma membrane for recognition by T cells.

Saposins are involved the lysosomal degradation of glycosphingolipids by glycosidic enzymes. Interestingly, this family of proteins has also recently been shown to be involved in the loading of lipid antigens into CD1 molecules.

CD1-restricted T cells can be activated by the presentation of cognate microbial antigens or by an indirect mechanism that involves Toll-like receptor stimulation and secretion of interleukin-12, which amplifies the weak CD1-restricted self-lipid reactivity and ensures a rapid activation of a large pool of NKT cells.

This Review describes the journey taken by the MHC-class-I-like CD1 molecules, detailing their assembly, intracellular trafficking and loading with lipid antigens. By taking distinct routes, the different CD1-family members ensure that each intracellular compartment is surveyed for their lipid cargo.