Cytoplasmic Tail-Dependent Localization of CD1b Antigen-Presenting Molecules to MIICs

Sugita, Masahiko; Jackman, Robin M.; Donselaar, Elly van; Behar, Samuel M.; Rogers, Rick A.; Peters, Peter J.; Brenner, Michael B.; Porcelli, Steven A.

doi:10.1126/science.273.5273.349

Cited by 220 publications

(153 citation statements)

References 30 publications

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“…Interestingly, this result parallels reported findings for a chimeric mouse MHC class II protein with a GPI anchor, which also demonstrated a significantly diminished ability to present Ags to restricted T cells (15). In fact, both CD1b and MHC class II molecules may load Ags in the same types of late endosomal compartments (13). Late endosomes are thought to possess a milieu amenable to the loading of CD1b with Ags, given their acidic pH and the presence of CD1b-binding Ags (11,13,14,30).…”

Section: Discussionsupporting

confidence: 87%

“…Recent experimental evidence suggests that the cytoplasmic domains of CD1 proteins influence their Ag-presenting functions by directing their distribution within the cell (11)(12)(13)27). For human CD1b and mouse CD1d1, deletion of the targeting motif disrupts .…”

Section: Discussionmentioning

confidence: 99%

“…Detailed studies have reported the subcellular distribution of human CD1b, the majority of which is localized inside the cell and is preferentially distributed within late endosomes or lysosomes. At this intracellular site CD1b most likely encounters and binds its cognate Ags (11)(12)(13)(14). Localization of CD1b to endosomal compartments is strongly dependent on the tyrosine-based motif in its short cytoplasmic tail.…”

Section: Glycosyl-phosphatidylinositol Reanchoring Unmasks Distinctmentioning

confidence: 99%

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Glycosyl-Phosphatidylinositol Reanchoring Unmasks Distinct Antigen-Presenting Pathways for CD1b and CD1c

Geho

Fayen

Jackman

et al. 2000

The Journal of Immunology

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Human CD1 proteins present lipid and glycolipid Ags to T cells. Cellular trafficking patterns of CD1 proteins may determine the ability of differing isoforms of CD1 to acquire, bind, and present these Ags to T cells. To test this hypothesis, glycosyl-phosphatidylinositol (GPI)-modified variants of CD1b and CD1c were engineered by chimerization with a GPI modification signal sequence derived from decay-accelerating factor (DAF). GPI reanchoring was confirmed by demonstrating the phosphatidylinositol-specific phospholipase C sensitivity of the CD1b · DAF and CD1c · DAF fusion proteins expressed on transfectant cell surfaces. Using cytotoxicity and cytokine release assays as functional readouts, we demonstrated that CD1c · DAF is as efficient as native CD1c in presenting mycobacterial Ags to the human CD1c-restricted T cell line CD8-1. In contrast, CD1b · DAF, although also capable of presenting Ag (in this case to the CD1b-restricted T cell line LDN5), was less efficient than its native CD1b counterpart. The data support the idea that CD1c · DAF maintains the capacity to access CD1c Ag-loading compartment(s), whereas CD1b · DAF is diverted by its GPI anchor away from the optimal CD1b Ag-loading compartment(s). This constitutes the first GPI reanchoring of CD1 proteins and provides evidence that CD1b and CD1c have nonoverlapping Ag-presenting pathways, suggesting that these two Ag-presenting molecules may have distinct roles in lipid Ag presentation.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Glycosyl-phosphatidylinositol Reanchoring Unmasks Distinctmentioning

confidence: 99%

See 1 more Smart Citation

Glycosyl-Phosphatidylinositol Reanchoring Unmasks Distinct Antigen-Presenting Pathways for CD1b and CD1c

Geho

Fayen

Jackman

et al. 2000

The Journal of Immunology

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“…In contrast, freshly isolated monocytes do not, or only occasionally, express CD1a, -b and -c ( [7,18] It is possible that the CD1 molecules, rather than acting as APC might function as cell-surface receptors, bringing exogenous antigens into the MHC class II compartment followed by MHC class II-mediated presentation of TT and PPD to T cells. CD1b molecules have been found in endosomal structures, predominantly in late endosomes, where they are co-localized with class II molecules [21,22]. Some recent data also indicates that mouse CD1 traf®cs to endosomal compartments where it can bind peptides derived from processed proteins [23].…”

Section: Discussionmentioning

confidence: 99%

Participation of CD1 Molecules in the Presentation of Bacterial Protein Antigens in Humans

Ulanova¹,

Tarkowski

Hahn-Zoric³

et al. 1999

Scand J Immunol

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Human CD1 molecules, expressed on the surface of professional antigen-presenting cells (including dendritic cells, Langerhans' cells, B cells and activated monocytes) are structurally homologous to major histocompatibility complex (MHC) class I and class II molecules. CD1b and CD1c have been shown to present nonpeptide bacterial antigens to T cells. We hypothesized that CD1 molecules may also be involved in the presentation of bacterial protein antigens. Human peripheral blood mononuclear cells (PBMC) were exposed to two medically important proteins, tetanus toxoid (TT) and puri®ed protein derivative (PPD), with and without murine monoclonal antibodies (MoAbs) speci®c for CD1a, CD1b and CD1c. All the MoAbs substantially inhibited the proliferative responses of PBMC to TT and PPD. Simultaneous interaction of CD1 and MHC class II molecules was even more inhibitory to these antigen-speci®c proliferative responses. In contrast, neither mixed lymphocyte reaction nor superantigen and mitogenic responses were affected by CD1-speci®c antibodies, indicating a certain restriction pattern in antigen presentation. Our ®ndings suggest that, besides MHC class I and II molecules, there is a family of nonpolymorphic cell surface molecules that is able to present certain bacterial protein antigens to T cells.

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“…Kawano and colleagues showed that chloroquine and concanamycin A, that prevent acidi®cation of and transportation to late endosomes, respectively, could inhibit presentation of aGalCer by dendritic cells [31], thus indicating a requirement for endosomal processing pathways. Further, CD1 has been found preferentially localized to the acidic endosomal compartments, including MHC class II-containing compartments (MIIC) [39,40]. Because B cells but not T cells express MHC class II, the presentation of exogenous aGalCer on A20 CD1 transfectants is expected to be more ef®cient.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2000

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The natural killer (NK) T-lymphocyte population consists of two subsets utilizing a diverse and restricted Tcell receptor (TCR) repertoire, respectively. Both populations have been shown to include autoreactive cells. NKT cells carrying restricted Va14(AV14S1)Ja281/Vb8.2(BV8S2A1) TCR have been shown to recognize a-galactosylceramide (aGalCer) presented in the context of murine CD1d. In this study we screened a set of murine CD1d-autoreactive T-cell hybridomas with diverse TCR for their reactivity with several glycosylated variants of ceramide, including aGalCer. These hybridomas showed a different pattern of reactivity to CD1d-expressing antigen-presenting cells (APC) and were not reactive with any of the tested variants of ceramide. A second set of hybridomas had been selected for expression of Va14 and Vb8.2 TCR chains. These cells responded to aGalCer presented on CD1d, but were only weakly reactive to syngeneic splenocytes or CD1d-transfected cells. Their ®ne speci®city in the response to glycosylation variants of ceramide demonstrated a homogenous reactivity pattern, including reactivity to a-galactosylsphingosine, the variant of aGalCer with truncated fatty acyl chain. These ®ndings underline the differences in ligand speci®city between the two subsets of CD1d-restricted NKT cells, and demonstrate a similarity in reactivity among the hybridomas using the Va14-Ja281/Vb8.2 TCR.

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Cytoplasmic Tail-Dependent Localization of CD1b Antigen-Presenting Molecules to MIICs

Cited by 220 publications

References 30 publications

Glycosyl-Phosphatidylinositol Reanchoring Unmasks Distinct Antigen-Presenting Pathways for CD1b and CD1c

Glycosyl-Phosphatidylinositol Reanchoring Unmasks Distinct Antigen-Presenting Pathways for CD1b and CD1c

Participation of CD1 Molecules in the Presentation of Bacterial Protein Antigens in Humans

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

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