Four pathways of CD1 antigen presentation to T cells

Moody, D. Branch; Cotton, Rachel N.

doi:10.1016/j.coi.2017.07.013

Cited by 45 publications

(44 citation statements)

References 61 publications

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“…Natural killer T cells were originally identified by the expression of NK markers as well as their TCR and later defined for their capacity to recognise lipid antigens presented by the MHC‐I‐like molecule CD1 . CD1 molecules encompass a family of lipid‐presenting proteins (CD1a‐d in humans, with only CD1d expressed in mice) that vary in the structure of their lipid‐binding grooves, patterns of cellular expression and intracellular trafficking . Within the thymus, CD1 + CD4 + CD8 + thymocytes participate in the selection of NKT cells that will consequently become CD1‐restricted .…”

Section: Nkt Cells: An Overviewmentioning

confidence: 99%

NKT cells and the regulation of intestinal immunity: a two‐way street

2020

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The mammalian gastrointestinal compartment is colonised by millions of microorganisms that have a central influence on human health. Intestinal homeostasis requires a continuous dialogue between the commensal bacteria and intestinal immune cells. While interactions between host and commensal bacteria are normally beneficial, allowing training and functional tuning of immune cells, dysregulated immune system-microbiota crosstalk can favour the development of chronic inflammatory diseases, as it is the case for inflammatory bowel disease (IBD). Natural killer T (NKT) cells, which recognise CD1-restricted microbial and self-lipids, contribute to the regulation of mucosal immunity by controlling intestinal homeostasis and participating in the development of IBD. Here, we provide an overview of the recently identified pathways underlying the crosstalk between commensal bacteria and NKT cells and discuss the effect of these interactions in intestinal health and disease.

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Section: Nkt Cells: An Overviewmentioning

confidence: 99%

NKT cells and the regulation of intestinal immunity: a two‐way street

2020

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“…CD1c and CD1d are expressed by B cells including leukaemic lymphoma cells . CD1a and to a lesser extent CD1c are expressed by skin‐resident Langerhans cells . The unique intracellular trafficking routes and cellular expression patterns within different tissues is consistent with a specialized role for each CD1 isotype.…”

Section: Unique Features Allow Diverse Lipid Samplingmentioning

confidence: 80%

“…Additionally, while CD1a, CD1b, CD1c and CD1d are expressed by myeloid dendritic cells, they all have niche cellular and tissue expression patterns. CD1d is constitutively expressed on many haematopoietic and non‐haematopoietic cells including epithelial cells . Whereas CD1a, CD1b and CD1c expression is restricted to professional APCs.…”

Section: Unique Features Allow Diverse Lipid Samplingmentioning

confidence: 99%

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The versatility of the CD1 lipid antigen presentation pathway

Chancellor¹,

Gadola

Mansour³

2018

Immunology

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The family of non-classical major histocompatibility complex (MHC) class-I like CD1 molecules has an emerging role in human disease. Group 1 CD1 includes CD1a, CD1b and CD1c, which function to display lipids on the cell surface of antigen-presenting cells for direct recognition by T-cells. The recent advent of CD1 tetramers and the identification of novel lipid ligands has contributed towards the increasing number of CD1-restricted T-cell clones captured. These advances have helped to identify novel donor unrestricted and semi-invariant T-cell populations in humans and new mechanisms of T-cell recognition. However, although there is an opportunity to design broadly acting lipids and harness the therapeutic potential of conserved T-cells, knowledge of their role in health and disease is lacking. We briefly summarize the current evidence implicating group 1 CD1 molecules in infection, cancer and autoimmunity and show that although CD1 are not as diverse as MHC, recent discoveries highlight their versatility as they exhibit intricate mechanisms of antigen presentation.

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“…CD1d undergoes complex cellular trafficking in a manner similar to that of MHC class II. Following synthesis in the endoplasmic reticulum, CD1d traffics via the Golgi apparatus to the plasma membrane, and is then internalised and trafficked through early and late endocytic compartments before being returned to the plasma membrane 5 , where CD1d-lipid complexes are recognized by the T cell receptor (TCR) of natural killer T (NKT) cells. Invariant NKT (iNKT) cells, which bear an invariant TCR and are characteristically potently activated by recognition of CD1d loaded with the synthetic glycolipid αgalactosylceramide (α-GalCer), are innate-like T cells involved in the orchestration of immune responses 6 .…”

Section: Introductionmentioning

confidence: 99%

The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading

Shamin

Benedyk

Graham

et al. 2019

Preprint

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Lipid antigens are presented on the surface of cells by the CD1 family of glycoproteins, which have structural and functional similarity to MHC class I molecules. The hydrophobic lipid antigens are embedded in membranes and inaccessible to the lumenal lipid-binding domain of CD1 molecules. Therefore, CD1 molecules require lipid transfer proteins for lipid loading and editing. CD1d is loaded with lipids in late endocytic compartments, and lipid transfer proteins of the saposin family have been shown to play a crucial role in this process. However, the mechanism by which saposins facilitate lipid binding to CD1 molecules is not known and is thought to involve transient interactions between protein components to ensure CD1-lipid complexes can be efficiently trafficked to the plasma membrane for antigen presentation. Of the four saposin proteins, the importance of Saposin B (SapB) for loading of CD1d is the most well-characterised. However, a direct interaction between CD1d andSapB has yet to be described. In order to determine how SapB might load lipids onto CD1d, we used purified, recombinant CD1d and SapB and carried out a series of highly sensitive binding assays to monitor direct interactions. Using equilibrium binding analysis, chemical cross-linking and cocrystallisation experiments, under a range of different conditions, we could not demonstrate a direct interaction. This work establishes comprehensively that the role of SapB in lipid loading does not involve direct binding to CD1d. We discuss the implication of this for our understanding of lipid loading of CD1d and propose several factors that may influence this process.

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Four pathways of CD1 antigen presentation to T cells

Cited by 45 publications

References 61 publications

NKT cells and the regulation of intestinal immunity: a two‐way street

NKT cells and the regulation of intestinal immunity: a two‐way street

The versatility of the CD1 lipid antigen presentation pathway

The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading

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