Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire

Makowska, Karolina; Kawano,; Taniguchi,; Cardell,

doi:10.1046/j.1365-3083.2000.00754.x

Cited by 35 publications

(28 citation statements)

References 23 publications

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“…The structural features of a-GalCer essential for efficient binding to CD1d and subsequent NKT cell stimulation have been the topic of interest in several studies [4,26,[36][37][38]. On the basis of these reports, it is clear that lipid chain length, although possibly contributing to CD1d binding, is not critical for efficient NKT cell stimulation.…”

Section: Discussionmentioning

confidence: 99%

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

et al. 2005

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The current consensus on characterization of NKT cells is based on their reactivity to the synthetic glycolipid, a-galactosylceramide (a-GalCer) in a CD1d-dependent manner. Because of the limited availability of a-GalCer, there is a constant search for CD1d-presented ligands that activate NKT cells. The a-anomericity of the carbohydrate is considered to be an important requisite for the CD1d-specific activation of NKT cells. The gram-negative, lipopolysaccharide-free bacterium Sphingomonas paucimobilis is known to contain glycosphingolipids (GSL) with a-anomeric sugars attached to the lipid chain. Here, we report that GSL extracted from this bacterium are able to stimulate NKT cells in a CD1d-specific manner. In addition, soluble CD1d-Ig dimers loaded with this lipid extract specifically bind to NKT cells (but not conventional T cells). Further studies on the S. paucimobilis GSL could potentially lead to other natural sources of CD1d-specific ligands useful for NKT cell analyses and aimed at identifying novel therapies for a variety of disease states. IntroductionLipid antigens, including phospholipids and glycosphingolipids (GSL), are presented by CD1d -a subset of the CD1 family of MHC class I-like molecules -to specialized immune effector cells called NKT cells [1]. Located on a different chromosome than the MHC, five different CD1 genes encode CD1 molecules -CD1a, CD1b, CD1c, CD1d and CD1e -in humans, whereas only two homologues of CD1d (CD1d1 and CD1d2) are present in mice [2]. On the basis of the crystal structure of mouse CD1d1 [3], it is predicted that the fatty-acyl chains are buried in the hydrophobic pocket of the molecule with the hydrophilic head-group of the lipid antigen available outside the molecule for its interaction with the NKT cell receptor. Even though the lipidbinding groove of CD1d is widely accommodative of many lipid groups, it is believed that only the sugar structures in a-anomeric orientation are able to stimulate NKT cells [4]. Because of the lack of physiological glycolipids with terminal a-anomeric sugars, it is hypothesized that both altered selfglycolipids during a pathological process and exogenous antigenic glycolipids could be potential ligands presented by CD1d [4]. The presence of GSL in the cell wall of some bacterial strains indicates the possibility of these bacterial GSL being presented by CD1d. Although human CD1a, b and c molecules are known to present mycobacterial antigens to human NKT cells, there is a lack of substantial evidence to show that CD1d has the ability to present these microbial lipids [5]. In a recent study, Fischer et al. [6] were able to show that mycobacterial phosphoinositolmannosides (PIM) could bind to soluble CD1d and activate human and mouse NKT cells. However, only a fraction of NKT cells detected by agalactosylceramide (a-GalCer) could be stained by a CD1d tetramer loaded with mycobacterial PIM [6]. A recent study [7] was able to show the binding of synthetic a-GalNAc containing GSL to cell surface CD1d, but no functional studies were done t...

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Section: Discussionmentioning

confidence: 99%

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

et al. 2005

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“…In line with this, recent reports have described ligand-specific reactivity to several distinct GPI molecules by NKT cells (3) and reactivity to cellular phospholipids (40), demonstrating the existence of a diversity of ligands recognized by CD1-restricted T cells. The 24␣␤ TCR recognizes a putative unknown CD1-bound ligand not requiring endosomal loading (41) and distinct from the ceramide based ligands activating the V␣14-type T cells (2,40,42,56).…”

Section: Discussionmentioning

confidence: 99%

CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR

Sköld

Faizunnessa

Wang

et al. 2000

The Journal of Immunology

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The majority of T lymphocytes carrying the NK cell marker NK1.1 (NKT cells) depend on the CD1d molecule for their development and are distinguished by their potent capacity to rapidly secrete cytokines upon activation. A substantial fraction of NKT cells express a restricted TCR repertiore using an invariant TCR Vα14-Jα281 rearrangement and a limited set of TCR Vβ segments, implying recognition of a limited set of CD1d-associated ligands. A second group of CD1d-reactive T cells use diverse TCR potentially recognizing a larger diversity of ligands presented on CD1d. In TCR-transgenic mice carrying rearranged TCR genes from a CD1d-reactive T cell with the diverse type receptor (using Vα3.2/Vβ9 rearrangements), the majority of T cells expressing the transgenic TCR had the typical phenotype of NKT cells. They expressed NK1.1, CD122, intermediate TCR levels, and markers indicating previous activation and were CD4/CD8 double negative or CD4+. Upon activation in vitro, the cells secreted large amounts of IL-4 and IFN-γ, a characteristic of NKT cells. In mice lacking CD1d, TCR-transgenic cells with the NKT phenotype were absent. This demonstrates that a CD1d-reactive TCR of the “non-Vα 14” diverse type can, in a ligand-dependent way, direct development of NK1.1+ T cells expressing expected functional and cell-surface phenotype characteristics.

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“…However, MZ B cells develop late in ontogeny in normal mice (13). In B6 mice, B cells of the CD21 high CD23 low or CD1d high phenotype start to appear as a distinct population after 3 wk of age, and the population reaches adult levels 7-8 wk after birth (30). In contrast, by 3 wk of age, a significant population (6 -8%) of B cells with the MZ phenotype (CD21 high CD23 low ) was present in NOD mice, whereas at this age the population was essentially undetectable in B6 mice (Fig.…”

Section: Mz B Cells Appeared Early During Nod Mouse Ontogenymentioning

confidence: 99%

The Enlarged Population of Marginal Zone/CD1dhigh B Lymphocytes in Nonobese Diabetic Mice Maps to Diabetes Susceptibility RegionIdd11

Rolf

Motta

Duarte

et al. 2005

The Journal of Immunology

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The NOD mouse is an important experimental model for human type 1 diabetes. T cells are central to NOD pathogenesis, and their function in the autoimmune process of diabetes has been well studied. In contrast, although recognized as important players in disease induction, the role of B cells is not clearly understood. In this study we characterize different subpopulations of B cells and demonstrate that marginal zone (MZ) B cells are expanded 2- to 3-fold in NOD mice compared with nondiabetic C57BL/6 (B6) mice. The NOD MZ B cells displayed a normal surface marker profile and localized to the MZ region in the NOD spleen. Moreover, the MZ B cell population developed early during the ontogeny of NOD mice. By 3 wk of age, around the time when autoreactive T cells are first activated, a significant MZ B cell population of adult phenotype was found in NOD, but not B6, mice. Using an F2(B6 × NOD) cross in a genome-wide scan, we map the control of this trait to a region on chromosome 4 (logarithm of odds score, 4.4) which includes the Idd11 and Idd9 diabetes susceptibility loci, supporting the hypothesis that this B cell trait is related to the development of diabetes in the NOD mouse.

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Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire

Cited by 35 publications

References 23 publications

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR

The Enlarged Population of Marginal Zone/CD1dhigh B Lymphocytes in Nonobese Diabetic Mice Maps to Diabetes Susceptibility RegionIdd11

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