Structure of an α-Helical Peptide and Lipopeptide Bound to the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule CD1d

Gottardi, Enrico; Wang, Jing; Zajonc, Dirk M.

doi:10.1074/jbc.m115.702118

Cited by 10 publications

(10 citation statements)

References 35 publications

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“…Whereas glycolipids, such as α-GalCer, deeply penetrate A 0 and F 0 pockets of CD1d (22). As there was competitive binding with α-GalCer, we thought that hSCP2 518-532 could be presented by CD1d adequately.…”

Section: Discussionmentioning

confidence: 91%

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Detection of Autoreactive Type II NKT Cells: A Pilot Study of Comparison Between Healthy Individuals and Patients with Vasculitis

et al. 2018

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NKT cells are defined as T cells that recognize hydrophobic antigens presented by class I MHC-like molecules, including CD1d. Among CD1d-restricted NKT cells, type I and type II subsets have been noted. CD1d-restricted type I NKT cells are regarded as proinflammatory cells in general. On the contrary, accumulated evidence has demonstrated an anti-inflammatory property of CD1d-restricted type II NKT cells. In our earlier study using a rat model with vasculitis, we demonstrated the pro-inflammatory function of CD1d-restricted type II NKT cells and identified that one such cell recognized P 518-532 of rat sterol carrier protein 2 (rSCP2 518-532 ), which appeared on vascular endothelial cells presented by CD1d. Based on this evidence, we attempted to detect human CD1d-restricted type II NKT cells in peripheral blood using hSCP2 518-532 , the human counterpart of rSCP2 518-532, together with a CD1d tetramer in flow cytometry. First, we determined the binding of hSCP2 518-532 to CD1d. Next, we detected CD3-positive hSCP2 518-532 -loaded CD1d (hSCP2 518-532 /CD1d) tetramer-binding cells in peripheral blood of healthy donors. The abundance of TGF-β-producing cells rather than TNF-α-producing cells in CD3-positive hSCP2 518-532 /CD1d tetramer-binding cells suggests the anti-inflammatory property of SCP2-loaded CD1d (SCP2/CD1d) tetramer-binding type II NKT cells in healthy individuals. Furthermore, we compared cytokine profile between healthy individuals and patients with vasculitis in a pilot study. Interestingly, the percentage of TGF-β-producing cells in SCP2/CD1d tetramerbinding type II NKT cells in vasculitic patients was significantly lower than that in healthy controls despite the greater number of these cells. Although further studies to clarify the mechanism and significance of this phenomenon are needed, SCP2/CD1d tetramer-binding type II NKT cells in peripheral blood should be examined in more detail to understand the pathophysiology of vasculitides in humans.

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Section: Discussionmentioning

confidence: 91%

“…X-ray analyses have demonstrated that peptides can bind into the cleft between the α1 and α2 helixes of CD1d like the binding to MHC. Whereas glycolipids, such as α-GalCer, deeply penetrate A 0 and F 0 pockets of CD1d (22). There is still another possibility of the higher affinity of hSCP2 518-532 than α-GalCer to CD1d.…”

Section: Discussionmentioning

confidence: 99%

Detection of Autoreactive Type II NKT Cells: A Pilot Study of Comparison Between Healthy Individuals and Patients with Vasculitis

et al. 2018

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“…A recent provocative report [98] has renewed interest into the possibility that CD1d-restricted T cells can react with peptides, a notion that has been entertained for over 20 years. Early studies provided evidence that mouse CD1d can present a variety of hydrophobic synthetic peptides with the common motif [FW]-X-X-[ILM]-X-X-W to CD1d-restricted T cells [99].…”

Section: Cd1dmentioning

confidence: 99%

“…Until the recent study by Girardi et al . [98], the exact location of peptide binding to CD1d has remained elusive. These investigators determined the crystal structure of the complex between mouse CD1d and the first peptide identified to bind CD1d, synthetic p99.…”

Section: Cd1dmentioning

confidence: 99%

Mechanisms and Consequences of Antigen Presentation by CD1

Kaer

Joyce

2016

Trends in Immunology

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The CD1 proteins are a family of non-polymorphic, MHC class I-related molecules that present lipid antigens to subsets of T lymphocytes with innate- or adaptive-like immune functions. Recent studies have provided new insight into the identity of immunogenic CD1 antigens and the mechanisms that control the generation and loading of these antigens onto CD1 molecules. Furthermore, substantial progress has been made in identifying CD1-restricted T cells and decoding the diverse immunological functions of distinct CD1-restricted T cell subsets. These findings shed new light on the contributions of the CD1 antigen presentation pathway to normal health and a diverse array of pathologies, and provide a new impetus for exploiting this fascinating recognition system for the development of vaccines and immunotherapies.

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“…2). Lipid antigens that have been crystallized bound to mouse or human CD1d include phosphatidylcholine (PC), acquired during expression of CD1d in insect cells (Giabbai et al 2005); C8-α-galactosylceramide (PBS-25) together with a C16 spacer lipid (Zajonc et al 2005a); α-galactosylceramide (α-GalCer) (Koch et al 2005) and α-galacturonosylceramide (GalAGsl) (Wu et al 2006); sulfatide (Luoma et al 2013; Zajonc et al 2005c); phosphatidylinositol-dimannoside (PIM-2) (Zajonc et al 2006); isoglobotrihexosyl ceramide (iGb3) (Zajonc et al 2008a); phenyl group-containing α-GalCer analogs C6Ph, C8Ph, C10Ph, and C8PhF (Schiefner et al 2009); short chain α-GalCer analog OCH (Sullivan et al 2010); Borrelia burgdorferi glycolipid 2c and 2f (BbGL-2c, -2f) (Wang et al 2010); tetra-myristoyl cardiolipin (Dieude et al 2011); Streptococcus pneumonia glucosyl-diacylglycerol (Glc-DAG-s2) (Kinjo et al 2011); ganglioside GD3 (Mallevaey et al 2011); lyso PC (Lopez-Sagaseta et al 2012); and even a synthetic peptide p99, as well as the related lipopeptide p99p (Girardi et al 2016). …”

Section: Human/mouse Cd1 Isotype-specific Adaptationsmentioning

confidence: 99%

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

Zajonc

2016

Immunogenetics

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Class I-like CD1 molecules are in a family of antigen-presenting molecules that bind lipids and lipopeptides, rather than peptides for immune surveillance by T cells. Since CD1 lacks the high degree of polymorphism found in their major histocompatibility complex (MHC) class I molecules, different species express different numbers of CD1 isotypes, likely to be able to present structurally diverse classes of lipid antigens. In this review, we will present a historical overview of the structures of the different human CD1 isotypes and also discuss species-specific adaptations of the lipid-binding groove. We will discuss how single amino acid changes alter the shape and volume of the CD1 binding groove, how these minor changes can give rise to different numbers of binding pockets, and how these pockets affect the lipid repertoire that can be presented by any given CD1 protein. We will compare the structures of various lipid antigens and finally, we will discuss recognition of CD1-presented lipid antigens by antigen receptors on T cells (TCRs).

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Structure of an α-Helical Peptide and Lipopeptide Bound to the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule CD1d

Cited by 10 publications

References 35 publications

Detection of Autoreactive Type II NKT Cells: A Pilot Study of Comparison Between Healthy Individuals and Patients with Vasculitis

Detection of Autoreactive Type II NKT Cells: A Pilot Study of Comparison Between Healthy Individuals and Patients with Vasculitis

Mechanisms and Consequences of Antigen Presentation by CD1

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

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