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)

Human CD1 form a group of nonpolymorphic leukocyte surface molecules with homology to major histocompatibility complex (MHC) proteins. Recent findings in human and in mouse demonstrate the capacity of CD1 molecules to present nonpeptide components like lipids or lipoglycans as well as peptides. We studied the involvement of beta 2-microglobulin (beta 2m) in expression of the classic human CD1 proteins CD1a, CD1b, and CD1c. The beta 2m-deficient human melanoma cell line FO-1 was transiently transfected with either CD1a, CD1b, or CD1c DNA alone, or in combination with beta 2m using the adenovirus-enhanced receptor-mediated transfer infection system. Only co-transfection of FO-1 cells with CD1+ beta 2m resulted in the detection of CD1 Ag by monoclonal antibodies (mAb). This indicated that CD1 mAb recognized determinants are dependent on beta 2m and raised the question whether beta 2m-free forms of CD1 can be expressed. Therefore, to visualize CD1 molecule expression independently of beta 2m, we expressed tagged recombinant forms. A full-length CD1b construct tagged at the very C terminus with a small peptide was transported to the plasma membrane only when beta 2m was co-transfected. beta 2m involvement in the transport of CD1 was confirmed by expression of soluble forms of CD1a, CD1b, and CD1c in three different cell types. Analogous to tagged full-length CD1b, secretion of the soluble CD1 constructs was strictly dependent on beta 2m. The soluble CD1 chimeras were secreted as complexes with endogenous beta 2m. Thus, similar to its role for MHC class I expression, beta 2m is essential for processing and surface transport of the classic human CD1 molecules CD1a, CD1b, and CD1c.
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PMID:Analysis of the requirement for beta 2-microglobulin for expression and formation of human CD1 antigens. 920 86

T-cell dependent immune response is initiated by dendritic cells, which are the only leucocytes able to prime naive CD4-positive T cells. Langerhans cells (LC) are dendritic cells characterized by their localization within the epidermis, their dendritic shape, and their expression of specific markers such as major histocompatibility complex (MHC) class II molecules, CD1a and S100 protein. We retrospectively studied the phenotype of LC in the skin of eight children with MHC class II deficiency (bare lymphocyte syndrome) after allogeneic bone marrow transplantation (BMT). The presence of donor-derived MHC class II positive LC within the epidermis was studied by immunohistochemistry on skin biopsies performed for the determination of graft-versus-host disease. MHC class II positive LC were undetectable in the epidermis of a child who did not engraft and of three children 13-18 d after HLA-mismatched BMT, despite engraftment. However, donor-derived MHC class II positive LC were detected in four children 9-43 d after HLA-identical BMT. Our results demonstrate that LC can differentiate or expand very quickly, as early as within 9 d after BMT.
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PMID:Detection of donor-derived Langerhans cells in MHC class II immunodeficient patients after allogeneic bone marrow transplantation. 926 54

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 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 purified protein derivative (PPD), with and without murine monoclonal antibodies (MoAbs) specific 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-specific proliferative responses. In contrast, neither mixed lymphocyte reaction nor superantigen and mitogenic responses were affected by CD1-specific antibodies, indicating a certain restriction pattern in antigen presentation. Our findings 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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PMID:Participation of CD1 molecules in the presentation of bacterial protein antigens in humans. 1052 Jan 78

Dendritic cells (DC) can be present at distinct stages of differentiation within the immune system. Sallusto and colleagues have recently described an in vitro culture system suitable for analyzing the maturation processes of DC (Sallusto and colleagues, J. Exp. Med. 1994;179:1109-1118). Monocytes cultured for 6 d in the presence of granulocyte macrophage colony-stimulating factor and interleukin-4 develop into immature DC with a high endocytic capacity but a low capacity to stimulate T cells. When challenged by lipopolysaccharide, these cells upregulate costimulatory molecules, express CD83, and become mature DC. CCR1 and CCR5 chemokine receptors are highly expressed on immature DC and downregulated on mature DC. This in vitro system was used to characterize human lung DC. Lung DC were shown to express some characteristics of in vitro immature DC. These are: (1) low expression of the costimulatory molecules CD40, CD80, and CD86; (2) poor expression of the differentiation marker CD83 and no CD1a; and (3) good capacity to incorporate dextran. Lung DC express moderate levels of CCR1 and CCR5. However, lung DC, like in vitro mature DC, express high levels of major histocompatibility complex Class II molecules, show low expression of CD14 and CD64, and are characterized by their high capacity to stimulate allogeneic T cells to proliferate during mixed leukocyte reactions (MLRs). Although lung DC express low levels of CD80 and CD86, the important role of these costimulatory molecules in inducing high MLR was demonstrated by using blocking antibodies. Therefore, while lung DC have overall a phenotype and an endocytic capacity close to in vitro immature DC, they share, like in vitro mature DC, a powerful capacity to stimulate T cells.
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PMID:Human lung dendritic cells have an immature phenotype with efficient mannose receptors. 1053 11

Mortality from measles virus (MV) infection is caused mostly by secondary infections associated with a pronounced immunosuppression. Dendritic cells (DCs) represent a major target of MV and could be involved in immunosuppression. In this study, human monocyte-derived DCs were used to demonstrate that DC apoptosis in MV-infected DC-T-cell cocultures is Fas mediated, whereas apoptotic T cells could not be rescued by blocking the Fas pathway. Two novel consequences of DC apoptosis after MV infection were demonstrated. (i) Fas-mediated apoptosis of DCs facilitates MV release, while CD40 activation enhances MV replication in DCs. Indeed, detailed studies of infectious MV release and intracellular MV nucleoprotein (NP) showed that inhibition of CD40-CD40L ligand interaction blocks NP synthesis. We conclude that the CD40 ligand expressed by activated T cells first enhances MV replication in DCs, and then Fas ligand produced by activated T cells induces Fas-mediated apoptosis of DCs, thus facilitating MV release. (ii) Not only MV-infected DCs but also bystander uninfected DCs undergo a maturation process confirmed by CD1a, CD40, CD80, CD86, CD83, and major histocompatibility complex type II labeling. The bystander maturation effect results from contact and/or engulfment of MV-induced apoptotic DCs by uninfected DCs. A model is proposed to explain how both a specific immune response and immunosuppression can simultaneously occur after MV infection through Fas-mediated apoptosis and CD40 activation of DCs.
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PMID:Consequences of Fas-mediated human dendritic cell apoptosis induced by measles virus. 1075 53

Antigen presentation by lung macrophages/dendritic cells (DC) is thought to be important in obliterative bronchiolitis/bronchiolitis obliterans syndrome (OB/BOS), which severely limits survival post-lung transplantation. However, a recent study found minimal numbers of DC in lung allografts. We looked at numbers and phenotype of macrophages/DC in lung allografts using endobronchial biopsy (EBB) and transbronchial biopsy (TBB) from 22 lung transplant patients. Biopsies were stained with monoclonal markers of DC (CD1a, RFD1, and major histocompatibility complex [MHC] Class II), and "suppressor macrophages" (RFD1 and RFD7). Dendritic cells were also stained for the costimulatory molecules CD80 and CD86. Significantly greater numbers of DC/high-power field (HPF) were seen in biopsies when we defined DC using dendritic morphology and Class II MHC expression instead of CD1a expression. Dendritic cell numbers were significantly higher in eight patients with OB/BOS compared with 14 stable patients. Fifty percent of DC expressed CD86 and 20% expressed CD80. There was no difference in CD80 or CD86 expression between OB/BOS patients and stable patients. There was no correlation between DC numbers and presence or absence of acute rejection (AR), and/or cytomegalovirus (CMV) pneumonitis on current or prior biopsies. There were significantly more MHC Class II DC in EBB compared with TBB. We found minimal staining for lung macrophages capable of suppressing T-cell inflammation. We conclude that studies of lung allografts may underestimate DC numbers if relying on CD1a as the sole marker of DC. DC are increased in patients with OB/BOS compared with stable patients. EBB may be more important than TBB in looking for inflammatory changes of OB. DC expressing costimulatory molecules are present in lung allografts, and costimulatory pathway blockade may be useful in human lung allografts. Also, the absence of "suppressor" macrophages may increase susceptibility of human lung allografts to the rejection process.
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PMID:Dendritic cells and macrophages in lung allografts: A role in chronic rejection? 1076 33

The ability of antigen-presenting cells to sample distinct intracellular compartments is crucial for microbe detection. Major histocompatibility complex class I and class II molecules sample the cytosol or the late endocytic compartment, allowing detection of microbial peptide antigens that arise in distinct intracellular compartments. In contrast, CD1a and CD1b molecules mediate the presentation of lipid and glycolipid antigens and differentially sample early recycling endosomes or late endocytic compartments, respectively, that contain distinct sets of lipid antigens. Here, we show that, unlike the other CD1 isoforms or major histocompatibility complex molecules that each sample restricted only intracellular compartments, CD1c is remarkable in that it distributes broadly throughout the endocytic system and is expressed in both recycling endosomes and late endocytic compartments. Further, in contrast to CD1b, which requires an acidic environment to function, antigen presentation by CD1c was able to overcome dependence on vesicular acidification. Because CD1c is expressed on essential antigen-presenting cells, such as epidermal Langerhans cells (in the absence of CD1b), or on B cells (without CD1a or -b), we suggest that CD1c molecules allow a comprehensive survey for lipid antigens throughout the endocytic system even in the absence of other CD1 isoforms.
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PMID:CD1c molecules broadly survey the endocytic system. 1089 Sep 14

Vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP) are neuropathies characterized by a T-lymphocyte infiltrate in the peripheral nerves. The microenvironment in which these T cells become activated, and the molecules and cells that play a role in this process are incompletely understood. Using immunohistochemical analysis, we studied the effect of the presence of adhesion, costimulatory and antigen-presenting molecules on different cell types as a precondition for local T-cell activation in human sural nerve biopsies of seven patients with CIDP, three patients with vasculitic neuropathy and three healthy controls. In biopsies from CIDP and vasculitic neuropathy patients, but not in those from healthy controls, Schwann cells expressed the adhesion/T-cell stimulatory molecule CD58 (LFA-3). The CD58 molecule was also present on endothelial cells of all vasculitic neuropathy patients and one CIDP patient. In biopsies from normal controls and patients, CD54 (ICAM-1) expression was detectable on microvascular endothelial cells. In addition, expression of the costimulatory molecule CD86 was detected on vascular tissue in patients with vasculitic neuropathy. Although macrophages were always present in all subjects, expression of the major histocompatibility complex (MHC)-like molecule CD1a by macrophages was restricted to biopsies from two CIDP patients and one vasculitic neuropathy patient. Unexpectedly, Schwann cells of a single vasculitis patient strongly expressed CD1b, a molecule involved in the presentation of self-glycolipids to T cells. Schwann cells in biopsies from patients and normal controls expressed high levels of the invariant chain, CD74, a molecule involved in the intracellular sorting of MHC class II molecules. There was no evidence for the presence of dendritic cells in sural nerve biopsies. These findings support a model in which T-cell activation can be initiated and/or perpetuated locally in sural nerve biopsies of patients with CIDP and vasculitic neuropathy, and predict an important role for Schwann cells and endothelial cells.
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PMID:Expression of accessory molecules for T-cell activation in peripheral nerve of patients with CIDP and vasculitic neuropathy. 1100 19

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


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