Mammalian CD1 and MR1 genes

Abstract

All higher vertebrates share the fundamental components of the adaptive immune system: the B cell receptor, the T cell receptor, and classical MHC proteins. At a more detailed level, their immune systems vary considerably, especially with respect to the non-polymorphic MHC class I-like proteins. In mammals, the CD1 family of lipid-presenting proteins is encoded by clusters of genes of widely divergent sizes and compositions. Another MHC class I-like protein, MR1, is typically encoded by a single gene that is highly conserved among species. Based on mammalian genomes and the available data on cellular expression profiles and protein structure, we review MR1 genes and families of CD1 genes in modern mammals from a genetic and functional perspective. Understanding the CD1 and MR1 systems across animal species provides insights into the specialized functions of the five types of CD1 proteins and facilitates careful consideration of animal models for human diseases in which immune responses to lipids and bacterial metabolites play a role.

Lipid-Reactive T Cells in Immunological Disorders of the Lung

“…However, CD1 molecules have some unique characteristics that distinguish them from MHC class I molecules. First, human CD1 genes are located on chromosome 1, whereas human MHC genes are located on chromosome 6 (in mice, CD1 genes are on chromosome 3 and MHC genes are on chromosome 17) ( 7 ). Second, CD1 molecules are less polymorphic.…”

“…While CD1 proteins are expressed in every mammalian species that was examined, humans express five isoforms of CD1, categorized as group 1 molecules (CD1a, CD1b, and CD1c), group 2 molecules (CD1d), and group 3 molecules (CD1e) ( 4 – 7 ). All CD1 molecules, apart from CD1e, display lipid antigens within their hydrophobic antigen-binding groove.…”

CD1: From Molecules to Diseases

“…CD1a, CD1b, and CD1c are not expressed in mice and rats 50 , so tractable small animal models for study of these three CD1 types in vivo were limited. However, guinea pigs express CD1a, CD1b, and CD1c 51 , allowing analysis of mycobacterial infection and vaccination 52 , 53 .…”

“…These studies are based on evidence that M. tuberculosis expresses many lipid antigens to which CD1-reactive T cells respond 76 , 77 and that transgenic expression of human CD1b in mice provides some mycobacterial containment in vivo 60 . As discussed above, guinea pigs express homologs for human CD1a, CD1b, and CD1c 50 , so they can serve as models to define vaccine-induced responses. Proof-of-concept studies show that immunization with mycolic acid, diacylated sulfoglycolipids, or phosphatidylinositol dimannosides reduced lung inflammation and provided some reduction in bacterial burden compared with unvaccinated animals 52 , 53 .…”

The CD1 family: serving lipid antigens to T cells since the Mesozoic era

“…Most CD1-restricted T cells express an antigen receptor (TCR) composed of an αβ heterodimer (Brigl and Brenner 2004), but T cells expressing an γδ (Luoma et al 2013; Uldrich et al 2013) or δ/αβ TCR (Pellicci et al 2014) have also been reported. Since the discovery of the human CD1 locus, CD1 has been found in many more species and each species expresses different numbers of CD1 genes (see also Reinink and Van Rhijn 2016). …”