The Mannose Receptor Delivers Lipoglycan Antigens to Endosomes for Presentation to T Cells by CD1b Molecules

Prigozy, Theodore I.; Sieling, Peter A.; Clemens, Daniel L.; Stewart, Phoebe L.; Behar, Samuel M.; Porcelli, Steven A.; Brenner, Michael B.; Modlin, Robert L.; Kronenberg, Mitchell

doi:10.1016/s1074-7613(00)80425-2

Cited by 306 publications

(215 citation statements)

References 29 publications

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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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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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“…The identification of the mannose receptor as an Ag-capture molecule suggests that this protein is an important participant in basic immunologic responses (4). As such, decreased mannose receptor expression could be advantageous for invading pathogens.…”

Section: Tat Expression Specifically Inhibits Mannose Receptor Promotmentioning

confidence: 99%

“…It appears to play a key role in host defense against invading pathogens by mediating internalization of these organisms (3) and by delivering foreign Ags to MHC IIcontaining compartments for subsequent Ag presentation (4). Thus, the mannose receptor is a key effector molecule in initiating an early immune response against invading pathogens.…”

mentioning

confidence: 99%

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HIV-1 Tat Represses Transcription from the Mannose Receptor Promoter

Caldwell¹,

Egan

Shepherd

2000

The Journal of Immunology

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The mannose receptor is expressed on mature macrophages and immature dendritic cells, and functions to mediate phagocytosis of pathogens and capture of Ags for delivery to MHC class II-containing intracellular compartments. It has been previously reported that HIV-1-infected macrophages have reduced functions associated with the mannose receptor, including impaired Pneumocystis carinii phagocytosis and mannosylated albumin uptake. Several HIV-1-derived proteins including the Tat protein have been shown to transcriptionally repress host cell genes. The present study was undertaken to define the role of the HIV-1-derived protein Tat in HIV-mediated mannose receptor down-regulation. Cotransfection of the human macrophage cell line U937 with a Tat expression vector and a mannose receptor promoter-luciferase reporter construct resulted in down-regulation of mannose receptor promoter activity. This repression was targeted to the basal promoter. Expression of either one- or two-exon Tat resulted in decreased promoter activity. The addition of the transactivation response element (TAR) sequence enhanced the Tat-mediated repression. Down-regulation was also seen when transfected cells were treated with exogenously added Tat protein. These results are consistent with a mechanism whereby Tat reduces mannose receptor promoter activity by interfering with the host transcriptional initiation machinery, potentially resulting in decreased levels of surface mannose receptor available for Ag or pathogen capture.

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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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The Mannose Receptor Delivers Lipoglycan Antigens to Endosomes for Presentation to T Cells by CD1b Molecules

Cited by 306 publications

References 29 publications

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

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

HIV-1 Tat Represses Transcription from the Mannose Receptor Promoter

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

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