The Third Way: Progress on pathways of antigen processing and presentation by CD1

Abstract

Summary CD1 proteins are a third family of antigen presenting molecules that bind bacterial and autologous lipid antigens for presentation to T cells. With the solution of the crystal structures of several complexes of CD1 molecules with lipids, a greater appreciation has been gained of the adaptability of CD1 in binding lipid antigens with diverse structural features. Biochemical studies of the interactions between the TCR and CD1-lipid complexes have revealed striking contrasts with TCR that bind to peptides presented by MHC-encoded class I and class II molecules. The sphingolipid activating proteins (SAP) have recently been found to facilitate the transfer of lipid antigens onto CD1 molecules. This helps to provide an explanation as to how the thermodynamic barrier, caused by loading hydrophobic lipid antigens in a hydrophilic environment, can be overcome. Mechanisms of CD1 endosomal trafficking are being delineated, including the means by which adaptor proteins induce the localization of some types of CD1 molecules to lysosomes, where they bind antigens. Unlike MHC class I and class II proteins, specialized molecules that function solely in chaperoning CD1 molecules, or in facilitating their antigen loading, have not been found. This suggests that the CD1 antigen presenting system, which diverged early in vertebrate evolution from MHC antigen presenting molecules, is a simpler system with a character closer to the primordial antigen presenting function.

Dendritic Cells: Activation and Maturation - Applications for Cancer Immunotherapy

“…CD1 molecules are divided into two groups based on sequence homology, with various specificities to lipid antigens [92]. Isoforms CD1a, CD1b and CD1c belong to one group and CD1d belongs to another group.…”

“…Similar to MHC class I molecules, CD1 subunits must be associated with β 2 -microglobulin for expression on the cell surface and subsequent recognition by T cells [10]. In view of intracellular trafficking, CD1 molecules traffic through the endocytic pathway, interacting with lipid antigens and presenting them to CD1-restricted T cells [92]. In humans, CD1 isoforms are selectively expressed according to DC subsets, for example, CD1a expression is characteristic for Langerhans cells [93].…”

Immunity at the Maternal–Fetal Interface

“…Innate and adaptive immunity act in synchrony to deliver security against foreign material. The APCs of the innate immune system uptake, process, and present the pathogenic antigen to the T cells of the adaptive immunity via MHC class I, class II or CD1 molecules and T cell activation follows (Lechler et al, 1996;Reyes et al, 1997;Lawton and Kronenberg, 2004;Trombetta and Mellman, 2005). This lymphocyte activation by the APCs in turn leads to production of cytokines, antibodies, and cytotoxicity.…”

CD1 and MHC II find different means to the same end

“…Mouse CD1d can be coimmunoprecipitated with Ii [5] and w5-10% of hCD1d associates with MHC II molecules in the ER [54]. This association could be observed when nonameric MHC II-Ii complexes [(ab) 3 Ii 3 ] were formed, however, no evidence was found for hCD1d associating with Ii alone. Cells expressing a tail-deleted mutant of mCD1d are unable to induce an autoreactive response from Va14 C -transgenic thymocytes, although introduction of Ii into the mutant cell line restored both this activity and endolysosomal localization [5].…”

“…Among the second category of class I-like molecules are the CD1 proteins [3], which present lipids rather than peptides. Lipid antigen recognition is important because microbial glycolipids are different from those in mammalian cells and lipid antigen recognition is probably an important component of host defense.…”