Mutation of a Positively Charged Cytoplasmic Motif within CD1d Results in Multiple Defects in Antigen Presentation to NKT Cells

Shin, Jung Hoon; Park, Ji Young; Shin, Yoonseok; Lee, Hyunji; Park, Yoon Kyung; Jung, Seonghoon; Park, Seho

doi:10.4049/jimmunol.1100236

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…The lack of antigenicity observed for lysolecithin (also known as lysophospatidylcholine) is likely the result of the drastically different polar moiety (a phosphorylcholine group) of this lipid compared to the other antigens carrying hexose sugars. Moreover, the differences in the antigen presentation between plate bound CD1d and antigen-presenting cells (APCs) suggests that APCs either process antigens into an inactive form or prevent their presentation at the cell surface, consistent with the reported requirement of mCD1d trafficking to the lysosomal compartment for type II NKT cell activation 22,34 .…”

Section: Resultssupporting

confidence: 58%

Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens

et al. 2012

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Glycolipids presented by the major histocompatibility complex class I (MHC I) homolog CD1d are recognized by natural killer T (NKT) cells characterized by either a semi-invariant (type I or iNKT) or a relatively variable (type II) T cell receptor (TCR) repertoire. Here we describe the first structure of a type II NKT TCR complexed with CD1d-lysosulfatide (LSF). Both TCR α and β chains contacted the CD1d molecule with a diagonal footprint, typical of MHC-TCR interactions, while the antigen was recognized exclusively with a single TCR chain, similar to the iNKT TCR. Type II NKT cells, therefore, recognize CD1d-sulfatide complexes with a distinct recognition mechanism characterized by features of both iNKT cells as well as conventional peptide-reactive T cells.

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Section: Resultssupporting

confidence: 58%

Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens

et al. 2012

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“…Indeed, similar trafficking was observed when MHC-II or Ii was overexpressed with CD1d-TD (60,67). However, CD1d-RATD traffic to lamp-1 + compartment regardless of the existence of MHC-II or Ii (66). Moreover, CD1d-TD trafficked to lamp-1 + compartment by overexpressed MHC-II or Ii showed recovered antigen presentation to type I NKT cells compared to CD1d-TD (60,67).…”

Section: Cd1d Presentation Pathwaysupporting

confidence: 53%

“…Moreover, CD1d-TD trafficked to lamp-1 + compartment by overexpressed MHC-II or Ii showed recovered antigen presentation to type I NKT cells compared to CD1d-TD (60,67). However, the antigen presentation ability of CD1d-RATD to type I NKT cells was not recovered even though CD1d molecules were highly accumulated in lamp-1 + compartment (66).…”

Section: Cd1d Presentation Pathwaymentioning

confidence: 90%

“…Recently, it has been shown that when three consecutive arginines of this motif in murine CD1d were replaced with non-charged alanines (CD1d-RA), antigen presentation ability of CD1d-RA to type I NKT cells was severely reduced either for endogenous self lipid antigen and exogenous lipid antigens even though CD1d molecules were highly accumulated in the endolysosomal (lamp-1 + ) compartments. Moreover, CD1d-RA also had a defect in antigen presentation to type II NKT cells (66).…”

Section: Cd1d Presentation Pathwaymentioning

confidence: 99%

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The effect of intracellular trafficking of CD1d on the formation of TCR repertoire of NKT cells

Shin¹,

Park²

2014

BMB Reports

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CD1 molecules belong to non-polymorphic MHC class I-like proteins and present lipid antigens to T cells. Five different CD1 genes (CD1a-e) have been identified and classified into two groups. Group 1 include CD1a-c and present pathogenic lipid antigens to αβ T cells reminiscence of peptide antigen presentation by MHC-I molecules. CD1d is the only member of Group 2 and presents foreign and self lipid antigens to a specialized subset of αβ T cells, NKT cells. NKT cells are involved in diverse immune responses through prompt and massive production of cytokines. CD1d-dependent NKT cells are categorized upon the usage of their T cell receptors. A major subtype of NKT cells (type I) is invariant NKT cells which utilize invariant Vα14-Jα18 TCR alpha chain in mouse. The remaining NKT cells (type II) utilize diverse TCR alpha chains. Engineered CD1d molecules with modified intracellular trafficking produce either type I or type II NKT cell-defects suggesting the lipid antigens for each subtypes of NKT cells are processed/generated in different intracellular compartments. Since the usage of TCR by a T cell is the result of antigen-driven selection, the intracellular metabolic pathways of lipid antigen are a key in forming the functional NKT cell repertoire. [BMB Reports 2014; 47(5): 241-248]

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“…The role of a major intracellular signaling molecule, PI3 kinase, was also established by employing the well-known inhibitor Wortmanin. In another study, the accumulation of CD1d in the lysosomal compartment owing to the lack of a triple arginine motif results in the inhibition of lipid presentation to both NKT cells without effecting cell surface CD1d expression (Shin et al 2012). In contrast, a truncated CD1d tail inhibits antigen presentation to type I but not type II NKTcells suggesting differential modes of cellular signaling for two subsets (Chiu et al 1999; Chiu et al 2002; Jayawardena-Wolf et al 2001).…”

Section: Antigen Processing and Presentation To Type II Nkt Cellsmentioning

confidence: 99%

Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset

Dasgupta

Kumar

2016

Immunogenetics

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Type II natural killer T cells (NKT) are a subset of the innate-like CD1d-restricted lymphocytes that are reactive to lipid antigens. Unlike the type I NKT cells, which express a semi-invariant TCR, type II NKT cells express a broader TCR repertoire. Additionally, other features, such as their predominance over type I cells in humans versus mice, the nature of their ligands, CD1d/lipid/TCR binding, and modulation of immune responses, distinguish type II NKT cells from type I NKT cells. Interestingly, it is the self-lipid-reactivity of type II NKT cells that has helped define their physiological role in health and in disease. The discovery of sulfatide as one of the major antigens for CD1d-restricted type II NKT cells in mice has been instrumental in the characterization of these cells, including the TCR repertoire, the crystal structure of the CD1d/lipid/TCR complex, and their function. Subsequently, several other glycolipids and phospholipids from both endogenous and microbial sources have been shown to activate type II NKT cells. The activation of a specific subset of type II NKT cells following administration with sulfatide or lysophosphatidylcholine (LPC) leads to engagement of a dominant immunoregulatory pathway associated with the inactivation of type I NKT cells, conventional dendritic cells, and inhibition of the proinflammatory Th1/Th17 cells. Thus, type II NKT cells have been shown to be immunosuppressive in autoimmune diseases, inflammatory liver diseases, and in cancer. Knowing their relatively higher prevalence in human than type I NKT cells, understanding their biology is imperative for health and disease.

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Mutation of a Positively Charged Cytoplasmic Motif within CD1d Results in Multiple Defects in Antigen Presentation to NKT Cells

Cited by 6 publications

References 32 publications

Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens

Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens

The effect of intracellular trafficking of CD1d on the formation of TCR repertoire of NKT cells

Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset

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