Polymorphisms in CD1d affect antigen presentation and the activation of CD1d-restricted T cells

Abstract

CD1 proteins constitute a distinct lineage of antigen-presenting molecules specialized for the presentation of lipid antigens to T cells. In contrast to the extensive sequence polymorphism characteristic of classical MHC molecules, CD1 proteins exhibit limited sequence diversity. Here, we describe the identification and characterization of CD1d alleles in wild-derived mouse strains. We demonstrate that polymorphisms in CD1d affect the presentation of endogenous and exogenous ligands to CD1d-restricted T cells, including type I (V␣14i) and type II (non-V␣14i) natural killer T (NKT) cells. Using congenic mice, we found CD1d polymorphisms affect the thymic selection of type I NKT cells and induce allogeneic T cell responses. Collectively, results from these studies demonstrate a role for polymorphisms in influencing the development and function of CD1d-restricted T cells.T cell activation ͉ T cell development

Genetic control of murine invariant natural killer T-cell development dynamically differs dependent on the examined tissue type

“…Polymorphisms in the CD1d1 gene found in wild-derived inbred strains of Mus spretus and Mus musculus castaneus origins affect its antigen presentation function 40 . When congenically expressed in C57BL/6 mice, Mus spretus -derived CD1d1 molecules had a diminished ability to select iNKT-cells resulting a ~50% reduction of these cells in the thymus 40 . Therefore, the allele difference in CD1d1 could contribute to the overall low frequencies of iNKT-cells in the wild-derived inbred strains examined here.…”

The processing and presentation of lipids and glycolipids to the immune system

“…It is likely that CD1 evolution and its selection under infectious pressure obeys the very same rules that govern classical MHC evolution with the caveat that CD1 genes are not in a hot spot of recombination/mutagenesis like MHC genes. However, the polymorphism found in mouse CD1d genes both in non-coding(13) and in coding regions of the gene(14) has functional consequences that support this general idea that selective pressure applies to CD1 genes as it does on MHC genes.…”

Lipid antigens in immunity

“…In contrast to the polymorphic nature of classical MHC class I, CD1 genes exhibit little sequence diversity with few nonsynonymous single-nucleotide polymorphisms (Zimmer et al, 2009; Seshadri et al, 2013). All mammalian species investigated so far express at least one CD1 protein, suggesting conservation of the CD1 system in mammals (Kasmar et al, 2009).…”