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)

There is increasing evidence that ex vivo generated Langerhans cells (LCs) cannot fully substitute for their physiological counterparts in normal epidermis when studying the immunobiology of this prototype of a tissue-residing immature dendritic cell (DC). Here, we present CD1-based magnetic-activated cell-sorting (MACS) protocols for the effective isolation of human epidermal LCs. CD1c selection yielded a homogeneous population of pure and viable HLA-DR(+)/CD1a(+) DCs, with the ultrastructural features, surface antigen expression and cytokine profile, characteristic of epidermis-resident immature LCs. The immature state and functional integrity were established by allogeneic mixed lymphocyte reactions showing a weak stimulatory capacity of freshly isolated cells and upregulation upon stimulation. Characterizing the cells in more detail, we could demonstrate for the first time that normal human LCs express CXCR4, CD40 ligand (CD40L), and Fas and Fas ligand (FasL). The observed constitutive transcription of TGF-beta suggests that the viability and immature state of epidermal LCs are maintained not only by the TGF-beta production from the microenvironment, but also in an autocrine or paracrine manner. LPS and IFN-omega stimulated the expression of the inflammatory cytokines TNF-alpha and IL-1beta, and there was secretion of IL-12p70 after CD40 ligation. Remarkably, the CD1-sorted LCs showed no loss of their Birbeck granules and CD1a expression upon culturing and no spontaneous phenotypic and functional maturation into potent antigen-presenting cells (APCs). We conclude that human epidermal LCs obtained by the CD1c cell-sorting protocol are optimal candidates with which to elucidate the properties and capabilities of immature cells and to develop immunotherapeutic vaccines.
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PMID:CD1a and CD1c cell sorting yields a homogeneous population of immature human Langerhans cells. 1296 46

Dendritic cells (DCs) are a heterogeneous population of cells of fundamental importance in initiating innate as well as specific immune responses. The identity and function of DCs in the cat are unknown, although they are likely pivotal in the response to infection. In this study, feline DCs were derived by 3-10-day culture of adherent blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) in the presence of IL 4 and GM-CSF. BMMC consistently yielded a greater number of DCs than PBMC, and there were fewer macrophages than DC from both compartments. DCs expressed a distinct constellation of surface molecules, which included CD1a, CD1b, and CD1c, CD11b, CD14, and 2-3-fold higher levels of MHC class I and II molecules than co-cultured macrophages or fresh blood monocytes. DCs displayed typical cytoplasmic processes, limited non-specific esterase activity, and acquired antigen by phagocytosis, pinocytosis, and binding to specific receptors. Cytokine-exposed cells induced proliferation of allogeneic lymphocytes. Thus, the cells derived by these culture conditions had markers and functions analogous to immature myeloid DCs. Availability of feline DCs will enable investigation of their role in infectious disease and their potential therapeutic application.
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PMID:Immunophenotype and functional properties of feline dendritic cells derived from blood and bone marrow. 1452 31

The CD1 family consists of lipid antigen-presenting molecules, which include group I CD1a, CD1b, and CD1c and group II CD1d proteins. Topologically, they resemble the classical peptide antigen-presenting MHC molecules except that the large, exclusively nonpolar and hydrophobic, antigen-binding groove of CD1 has evolved to present cellular and pathogen-derived lipid antigens to specific T lymphocytes. As an approach to understanding the biochemical basis of lipid antigen presentation by CD1 molecules, we have characterized the natural ligands associated with mouse CD1d1 as well as human CD1b and CD1d molecules. We found that both group I and II CD1 molecules assemble with cellular phosphatidylinositol (PI), which contains heterogeneous fatty acyl chains. Further, this assembly occurs within the endoplasmic reticulum. Because the structures of the antigen-binding grooves of CD1a and CD1c closely resemble those of CD1b and CD1d, we conclude that the assembly of CD1 molecules with PI in the endoplasmic reticulum is evolutionarily conserved. These findings suggest that PI plays a chaperone-like role in CD1 assembly, possibly to preserve the integrity of the antigen-binding groove until CD1 binds antigenic lipids in the endocytic pathway.
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PMID:Lipid-protein interactions: biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved. 1472 59

Recent studies of CD1 structure and intracellular trafficking have demonstrated significant differences among the CD1 isoforms (CD1a, CD1b, CD1c and CD1d). The molecular and structural basis for the differential trafficking of CD1 molecules has also been delineated. These observations broaden our understanding of why the immune system has evolved multiple CD1 isoforms to survey different cellular compartments for lipid antigen presentation, to provide host defense against the microbial world and to offer immunoregulation with relevance to tumor immunity and autoimmunity.
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PMID:New insights into pathways for CD1-mediated antigen presentation. 1473 15

This review summarizes the major features of CD1 genes and proteins, the patterns of intracellular trafficking of CD1 molecules, and how they sample different intracellular compartments for self- and foreign lipids. We describe how lipid antigens bind to CD1 molecules with their alkyl chains buried in hydrophobic pockets and expose their polar lipid headgroup whose fine structure is recognized by the TCR of CD1-restricted T cells. CD1-restricted T cells carry out effector, helper, and adjuvant-like functions and interact with other cell types including macrophages, dendritic cells, NK cells, T cells, and B cells, thereby contributing to both innate and adaptive immune responses. Insights gained from mice and humans now delineate the extensive range of diseases in which CD1-restricted T cells play important roles and reveal differences in the role of CD1a, CD1b, and CD1c in contrast to CD1d. Invariant TCR alpha chains, self-lipid reactivity, and rapid effector responses empower a subset of CD1d-restricted T cells (NKT cells) to have unique effector functions without counterpart among MHC-restricted T cells. This review describes the function of CD1-restricted T cells in antimicrobial responses, antitumor immunity, and in regulating the balance between tolerance and autoimmunity.
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PMID:CD1: antigen presentation and T cell function. 1503 98

Anticancer immunotherapy using dendritic cell-based vaccines is a strategy aimed at the induction and maintenance of immune responses against cancer cells. Clinical applications of dendritic cells (DCs) require stringent adherence to Good Manufacturing Practice (GMP) methods and rigorous standardization of DC-based vaccine preparation. Recently, closed systems for DC culture have been developed with a goal to minimize the risk of contamination. Here, we compare the yield, immunophenotype, and functional properties of DCs generated in Lifecell X-Fold culture bags and in plastic wells, both from adherence-selected monocytes, and review the current literature on closed systems for DC generation. We found that both the overall yield and the yield of CD83+ cells in cell culture bags was lower than in the standard culture method. No statistically significant differences were observed in the expression of DC immunophenotypic markers. The capability of DCs cultured in bags and in wells to induce the proliferation of allogeneic mononuclear cells were equivalent. The performance of DCs in mixed lymphocyte reaction correlated significantly (p = 0.005) with the CD83 expression but not with the CD80, CD86, HLA-DR, CD1a, and CD1c expression. We conclude that the immunophenotype and stimulatory properties of DCs cultured in closed cell culture bags are similar to those generated by conventional method using cell culture wells.
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PMID:Generation of dendritic cells using cell culture bags--description of a method and review of literature. 1520 1

Human CD1 group I molecules CD1a, b, and c are expressed on antigen-presenting cells, notably dendritic cells, and implicated in glycolipids presentation to T lymphocytes. Expression of CD1 on monocytes is a hallmark of their activation. Because monocyte activation has been reported during steady state disease in sickle cell anemia (SCA) patients, we have analyzed CD1 expression on monocytes from 45 SCA patients originating from Africa and 27 healthy control subjects. CD1 expression was detected on monocytes in the majority of SCA patients (75%), whereas it was not observed in the vast majority of the control group (70.4%). CD1b and CD1c were highly expressed in Sbeta thalassemia patients and CD1a expression was predominant in SDPunjab patients. This expression of the CD1 molecules is correlated with an increased expression of the major histocompatibility complex class II invariant chain (CD74). Finally, we have observed that the majority of SCA patients (68%) express only two or one CD1 isoforms. This study demonstrates the particular phenotype of SCA monocytes intermediate between normal resting and activated monocytes, a phenotype that could have consequences on regulation of the infection outcome.
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PMID:Upregulation and atypical expression of the CD1 molecules on monocytes in sickle cell disease. 1555 87

CD1 molecules are expressed by antigen-presenting cells such as dendritic cells and mediate primary immune responses to lipids and glycolipids which have been shown to be expressed by various tumors. Glycolipids are expressed by melanoma cells but, despite their immunogenicity, no efficient spontaneous immune responses are elicited. As IL-10 has previously been shown to down-regulate CD1a on dendritic cells and is known to be expressed by various melanoma cell lines, we investigated if melanoma-derived IL-10 could down-regulate CD1 molecule expression on dendritic cells as a possible way to circumvent immune recognition. We found that CD1a, CD1b, CD1c, and CD1d were significantly down-regulated on dendritic cells in metastatic (n = 10) but not in primary melanoma lesions (n = 10). We further detected significantly higher IL-10 protein levels in metastatic than in primary melanomas. Moreover, supernatants from metastatic melanomas were significantly more effective in down-regulating CD1 molecules on dendritic cells than supernatants from primary melanoma cultures. This effect was blocked using a neutralizing IL-10 antibody in a dose dependent manner. Our findings suggest that metastatic but not primary melanomas can down-regulate CD1 molecules on infiltrating dendritic cells by secreting IL-10 which may represent a novel way to escape the immune response directed against the tumor.
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PMID:Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic cells in metastatic tumor lesions. 1557 30

There have been many reports studying the presentation for lipid antigen by CD1 molecules on dendritic cells (DC), mainly in the infection of acid-fast bacilli. But little is known about the expression of CD1 molecules in sarcoidosis. In this study, we analyzed the expression of CD1 molecules by immunohistochemical stain with monoclonal anti-CD1a, CD1b and CD1c antibody for the specimens of nine sarcoidosis patients (sarcoidosis group) and seven control cases (control group). Aggregation of CD1 positive cells was present adjacent to granulomas in five cases of the sarcoidosis group, but was absent in all cases of the control group. There were no differences in the results of laboratory findings or disease activity between CD1-positive and negative cases in the sarcoidosis group. These data suggest that the presentation of lipid antigens mediated by CD1 molecules on DC is involved in granuloma formation in sarcoidosis.
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PMID:[Analysis of CD1 molecules in the process of granuloma formation with sarcoidosis]. 1570 47

Molecular studies have shown that CD1 proteins present self and foreign lipid Ags to T cells, but the possible roles of CD1 in human autoimmune diseases in vivo are not known, especially for the group 1 CD1 isoforms (CD1a, CD1b, and CD1c). To investigate the hypothesis that CD1-restricted T cells might be activated and home to target tissues involved in Hashimoto's thyroiditis and Graves' disease, we performed ex vivo analysis of lymphocytes from peripheral blood and autoinflammatory lesions of thyroid tissue. Immunofluorescence analysis identified two types of CD1-expressing APCs in inflamed thyroid tissues. CD1a, CD1b, and CD1c were expressed on CD83+ dendritic cells, and CD1c was expressed on an abundant population of CD20+ IgD+ CD23- CD38- B cells that selectively localized to the mantle zone of lymphoid follicles within the thyroid gland. CD1c-restricted, glycolipid-specific T cells could not be detected in the peripheral blood, but were present in polyclonal lymphocyte populations isolated from affected thyroid glands. In addition, polyclonal thyroid-derived lymphocytes and short-term T cell lines were found to recognize and lyse targets in a CD1a- or CD1c-dependent manner. The targeting of CD1-restricted T cells and large numbers of CD1-expressing APCs to the thyroid gland during the early stages of autoimmune thyroiditis suggests a possible effector function of CD1-restricted T cells in tissue destruction and point to a new model of organ-specific autoimmune disease involving lipid Ag presentation.
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PMID:CD1a and CD1c activate intrathyroidal T cells during Graves' disease and Hashimoto's thyroiditis. 1574 18


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