The evolved functions of CD1 during infection

Abstract

CD1 proteins display lipid antigens to T cell receptors. Studies using CD1d tetramers and CD1d-deficient mice provide important insight into the immunological functions of invariant NK T cells (iNKT) during viral and bacterial infections. However, the mouse CD1 locus is atypical because it encodes only CD1d, whereas most mammalian species have retained many CD1 genes. Viewed from the perspective that CD1 is a diverse gene family that activates several of classes of T cells, new insights into lipid loading and infection response are emerging.

Figure 1. Structural homologies among CD1 ligands

Invariant NK T cells recognize structurally related glycolipid antigens that differ in the composition of their lipid anchors, but shared an α-linked galactose unit. Three types of mycobacterial mycolate antigens are recognized by CD1b-restricted T cells. These foreign molecules have lipid anchors (C72-86) that are much larger than most self diacylglycerols or sphingolipids. CD1b is the only CD1 protein that is known to have a groove large enough to accept this type of antigen.

Figure 2. Humans, cows and mice reflect differing patterns of CD1 gene conservation among mammalian species

Among CD1 restricted T cells, humans have NKT and non-NKT cells, whereas mice have only NKT cells, and cows have only non-NKT cells. Recent data suggest that the average number of CD1 genes in mammalian species is higher than in humans, so the mouse and other muroid rodents are distinctly atypical. CD1d1 and CD1d2 are highly homologous, but the three bovine genes that belong to the CD1b group have differing cytoplasmic tail sequences and differences in α1 and α2 domains that likely affect groove structure. This figure does not show the two bovine CD1b and the two bovine CD1d pseudogenes because they are predicted not to be translated into proteins.