Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The non-major histocompatibility complex (MHC)-encoded CD1 family has recently emerged as a new antigen-presenting system that is distinct from either MHC class I or class II molecules. In the present study, we determined the genomic structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes, especially to CD1D1. The 5' flanking region of the CD1 gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6. Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. It is of interest that a tyrosine-based motif for endosomal localization found in the human CD1b cytoplasmic tail was encoded by a single short exon which was conserved in all CD1 molecules except for CD1a. Southern blot and direct sequencing analyses of inbred rat strains suggested very limited polymorphism in the 5' region where a hydrophobic ligand-binding groove is encoded; a single base substitution resulted in amino acid alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the overall exon-intron organization of CD1 genes revealed that the length of the intron was also characteristic to each of the two classes of CD1 genes, classic CD1 and CD1D; such categorization has hitherto been made according to the sequence similarity of the coding region. This finding provides further support for the hypothesis that the two classes have different evolutionary histories. In contrast to the complete absence of the classic CD1 in rats and mice, the entire region of nonpolymorphic CD1D has been conserved through mammalian evolution. Similar functional properties of rodent CD1 and human CD1d are implied.
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PMID:Structural organization of rat CD1 typifies evolutionarily conserved CD1D class genes. 960 40

Human CD1 genes have been reported to be invariant or to show limited polymorphism. Recently, certain functions of CD1 antigens have been described to include the presentation lipid and glycolipid antigens. These observations prompted a thorough survey of the genetic polymorphism in the five human CD1 genes (CD1a-CD1e). Using polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) combined with sequence analyses, exons 2 and 3 from CD1a-CD1e were characterized from a total of 110 unrelated healthy donors. Results showed that all five genes (CD1a-CD1e) are polymorphic in exon 2. Substitutions in CD1b and CD1c are silent, whereas, substitutions in CD1a, CD1d and CD1e result in amino acid replacements in the deduced protein products. CD1a and CD1e polymorphisms are prevalent in the population. The substitutions in CD1a have characteristics that may influence interactions with beta2-microglobulin beta2-m) or accessory molecules. The substitution in CD1e is located in the region predicted to interact with ligands and may differentially impact the ability of CD1e alleles to bind antigen.
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PMID:Polymorphism of human CD1 genes. 1048 38

The intestinal epithelium is anatomically positioned to serve as the critical interface between the lumen and the mucosal immune system. In addition to MHC class I and II antigens, intestinal epithelia constitutively express the nonclassical MHC molecule CD1d, a transmembrane molecule with a short cytoplasmic tail expressed as a beta(2)-microglobulin-associated 48-kDa glycoprotein and novel beta(2)-microglobulin-independent 37-kDa nonglycosylated protein on intestinal epithelia. At present, it is not known whether extracellular ligands can signal intestinal epithelial CD1d. To define signaling of CD1d cytoplasmic tail, retrovirus-mediated gene transfer was used to generate stable cell lines expressing wild-type CD1d or a chimeric molecule (extracellular CD1d and cytoplasmic CD1a), and surface CD1d was triggered by antibody crosslinking. Although wild-type CD1d was readily activated (tyrosine phosphorylation), no demonstrable signal was evident in cell lines expressing the chimeric molecule. Subsequent studies revealed that anti-CD1d crosslinking specifically induces epithelial IL-10 mRNA and protein and is blocked by the tyrosine kinase inhibitor genistein. Further studies addressing epithelial-derived IL-10 revealed that anti-CD1d crosslinking attenuates IFN-gamma signaling and that such attenuation is reversed by addition of functionally inhibitory IL-10 antibodies. These results define signaling through surface CD1d, and, importantly, they demonstrate that this pathway may serve to dampen epithelial proinflammatory signals.
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PMID:Ligation of intestinal epithelial CD1d induces bioactive IL-10: critical role of the cytoplasmic tail in autocrine signaling. 1057 Jan 77

The CD1 family of proteins mediates a newly described pathway for presentation of lipids and glycolipids for specific recognition by T cells. All four of the known human CD1 proteins (CD1a, CD1b, CD1c and CD1d) as well as murine CD1d have now been shown to mediate T-cell recognition of lipid or glycolipid antigens. These antigens include naturally occurring foreign glycolipids from intracellular pathogens or synthetic glycolipids that are related in structure to mammalian glycolipids. The CD1b and CD1d-presented antigens differ in their fine structures but reveal a general motif in which a rigid hydrophilic cap is bound to two aliphatic hydrocarbon chains. Different T-cell populations recognize individual antigens without cross-reactivity to closely related antigen structures or CD1 isoforms, documenting the complexity and fine specificity of CD1-mediated T-cell responses. Mapping of the molecular determinants of recognition for CD1b and CD1d-presented antigens reveals that T cells discriminate the fine structure of the hydrophilic cap of the antigen, but both the length and structure of the lipid chains may be altered without loss of recognition. This pattern of lipid antigen recognition may be accounted for by a simple molecular mechanism of presentation that parallels the known mechanism for presentation of peptides, but solves the special problems related to the hydrophobic chemical nature of the lipid antigens. We propose that CD1 binds antigen by accommodating the two lipid tails within the hydrophobic groove of its two membrane distal domains, positioning the rigid hydrophilic cap of the antigen on the solvent-exposed surface of the CD1 protein, where it can directly contact the T-cell antigen receptor. This model provides a molecular basis for recognition of a new and diverse set of T-cell antigens contained within the lipid bilayers of cellular membranes.
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PMID:The molecular basis of CD1-mediated presentation of lipid antigens. 1063 54

Human T cells expressing CD161 and an invariant T-cell receptor (TCR) alpha-chain (Valpha24invt T cells) specifically recognize CD1d and appear to have immunoregulatory functions. However, the physiological target cells for this T-cell population, and whether alterations in CD1d expression contribute to the regulation of Valpha24invt T-cell responses, remain to be determined. A series of antibodies were generated to assess CD1d expression, structure and regulation on human lymphoid and myeloid cells. CD1d was expressed at high levels by human cortical thymocytes and immunoprecipitation analyses showed it to be a 48 000-MW glycosylated protein. However, after solubilization, the majority of the thymocyte CD1d protein, but not CD1d expressed by transfected cells, lost reactivity with monoclonal antibodies (mAbs) against native CD1d, indicating that it was alternatively processed. Moreover, thymocytes were not recognized by CD1d-reactive Valpha24invt T-cell clones. Medullary thymocytes and resting peripheral blood T cells were CD1d-, but low-level CD1d expression was induced on activated T cells. CD1d was expressed by B cells in peripheral blood and lymph node mantle zones, but germinal centres were CD1d-. Resting monocytes were CD1d+ but, in contrast to CD1a, b and c, their surface expression of CD1d was not up-regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) activation. These results demonstrate constitutive CD1d expression by human professional antigen-presenting cells and that post-translational processing of CD1d may contribute to regulation of the activity of CD1d-specific T cells.
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PMID:CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes. 1080 57

During the last decade the CD1 family of cell surface glycoproteins has been implicated in the presentation of nonpeptide antigens in man. Recent findings by our group indicate that CD1 molecules also can be involved in the presentation of certain bacterial proteins. However, CD1a, b, and c (group 1 CD1 molecules) are not present at significant levels on circulating monocytes unless their expression is induced by cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF). In this study we investigated the cell surface expression of CD1 molecules following the antigenic stimulation in vivo via immunization of healthy volunteers with tetanus toxoid vaccine and in vitro cell cultures using the same antigen. Both the in vivo and in vitro studies demonstrated clear up-regulation of the surface expression of CD1a, b, and c on monocytes as a result of antigenic stimulation with tetanus toxoid, supporting the idea that CD1 molecules participate in the presentation of this protein antigen in man. In vitro, antigen-triggered expression of these molecules was mediated by GM-CSF, since neutralization of this cytokine with specific antibody totally abrogated CD1a, b, and c expression. In contrast to the group 1 CD1 molecules, CD1d was found to be constitutively expressed on the majority of circulating monocytes and B lymphocytes prior to immunization. There was no effect of antigenic stimulation with tetanus toxoid on the cell surface expression of CD1d, suggesting major differences in regulation of the expression and function of the different CD1 molecules in humans. Altogether our results point to antigen-driven up-regulation of CD1a, b, and c expression on human monocytes that is mediated by GM-CSF and no effect on CD1d expression.
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PMID:Antigen-specific regulation of CD1 expression in humans. 1094 28

Glycolipid-specific, CD1a-, b- and c-dependent cytotoxic T cells have recently been shown to be involved in the host response against tuberculosis. These CD1 molecules 'sample' mycobacterial glycolipids from different intracellular sites in the infected cell. Additionally, upon microbial encounter, CD1d-dependent natural killer T cells promptly produce cytokines and perform regulatory activities. Here, we discuss the intracellular localization of CD1 molecules and mycobacterial lipids and the role of CD1-mediated T-cell responses in mycobacterial infections.
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PMID:CD1 and CD1-restricted T cells in infections with intracellular bacteria. 1120 Dec 61

CD1 cell surface glycoproteins represent a family of non-major histocompatibility complex (MHC) encoded antigen-presenting molecules. All members of the CD1 family appear to mediate the recognition of microbial or endogenous lipid and glycolipid antigens. The recognition of CD1d by a unique subset of natural killer (NK) T cells that leads to rapid production of large amounts of both type 1 and type 2 cytokines can be augmented by some synthetic glycolipids. Because of the proposed role of such CD1d-restricted T cells in immunoregulation, we hypothesized that CD1d molecules participate in mucosal immune responses in patients with gastrointestinal symptoms owing to food hypersensitivity. Patients of that category represent a heterogeneous group in which poorly defined immunological mechanisms are believed to contribute to disease pathogenesis. The expression of CD1 in duodenal biopsy samples from six patients with verified intolerance to cow's milk and six healthy controls was studied by immunoperoxidase staining of cryostat sections using a panel of mouse monoclonal antibodies (MoAbs) specific for CD1a, b, c, and d. Large numbers of CD1d positive cells were found in the lamina propria of all the patients, both during the symptomatic and the asymptomatic periods, whereas healthy controls were virtually devoid of CD1d expression in the duodenum. The localization of CD1d positive cells corresponded to areas where B cells, plasma cells and dendritic cells (DC) were present. A positive correlation was found between the numbers of CD1d(+) and CD19(+) cells in the lamina propria. In contrast to previous reports, no CD1d expression was found on the epithelial cells. Although less numerous than CD1d(+) the CD1c(+) cells were also present in all the patients and in five out of six controls. No staining for CD1a or CD1b was detected in the duodenal biopsy samples from any of the subjects. The exclusive presence of CD1d in the duodenal lamina propria of the patients with cow's milk hypersensitivity might suggest the participation of these molecules in the pathogenesis of allergic reactions to food.
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PMID:Expression of CD1d in the duodenum of patients with cow's milk hypersensitivity. 1111 68

Four human CD1 isoforms (CD1a, -b,-c and -d) are now known to be antigen presenting molecules with the unique ability to present lipid antigens to T cells. CD1b and CD1d are found in acidic, late endocytic compartments, whereas CD1a and CD1c molecules accumulate at the plasma membrane and in early endosomes. Consistent with their differences in intracellular localization, most studies show antigen presentation by CD1b/CD1d to be dependent on endosomal acidification while CD1a/CD1c mediated antigen presentation is not. Taken together, recent advances in the analysis of CD1 molecules reinforce the hypothesis that the different CD1 isoforms are specialized to survey the lipid content of distinct intracellular compartments. This may help to explain the duplication and diversification of CD1 genes in humans and other mammalian species.
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PMID:Diversification of CD1 proteins: sampling the lipid content of different cellular compartments. 1114 57

CD1 proteins are a family of cell surface molecules that present lipid antigens to T cells. We investigated skin dendritic cells and monocyte-derived dendritic cells for expression of CD1 molecules using a panel of 10 different monoclonal antibodies focusing on the recently described CD1d molecule. By immunohistochemical analysis, CD1d expression in normal human skin was restricted to dendritic appearing cells in the papillary dermis mainly located in a perivascular localization. Langerhans cells did not show detectable CD1d expression in situ. Epidermal/dermal cell suspensions analyzed by flow cytometry demonstrated distinct subpopulations of HLA-DR positive dermal dendritic cells expressing CD1a, CD1b, and CD1c. CD1d was expressed on HLA-DRbright dermal antigen-presenting cells in dermal suspensions (16% +/- 3.6%), as well as on highly enriched dermal dendritic cells migrating out of skin explants (60.5% +/- 8.0%). Migrated mature dermal dendritic cells coexpressed CD83 and CD1d. Western blot analysis on microdissected skin sections revealed the presence of a 50-55 kDa CD1d molecule in dermis, suggesting that CD1d is highly glycosylated in skin. Both immature and mature monocyte-derived dendritic cells cultured in autologous plasma expressed CD1d molecules. In contrast, culture in fetal bovine serum downregulated CD1d expression. In conclusion, antigen-presenting cells in skin express different sets of CD1 molecules including CD1d and might play a role in lipid antigen presentation in various skin diseases. Differential expression of CD1 molecules depending on culture conditions might have an impact on clinical applications of dendritic cells for immunotherapy.
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PMID:Cd1d is expressed on dermal dendritic cells and monocyte-derived dendritic cells. 1156 62


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