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)

Beta 2-microglobulin (beta 2m) constitutes the common light chain of both the MHC-encoded HLA-ABC molecules and a group of structurally related glycoproteins recognized by antibodies of the first cluster of differentiation (CD1a, CD1b and CD1c). These CD1 antigens appear similar to murine T1 and Qa molecules in terms of structure and tissue distribution, although the question of inter-species homology is controversial. A further group of alloantigens expressed predominantly on T cells has been reported however, with immunogenetic characteristics more closely analogous to the murine T1/Qa system than the CD1 antigens, although their precise identity remains ill-defined. Having previously shown that malignant B cells may express membrane CD1c, we examined leukaemic B-cells corresponding to early lymphoblastic differentiation (null- and common acute lymphoblastic leukaemia) through to the terminal plasma cell stage for the expression of other non-HLA class I beta 2m-associated molecules. It was found that leukaemic B-cells at intermediate/late stages of differentiation, represented by non-Hodgkin's lymphoma (B-NHL) and 'hairy-cell' leukaemia (HCL), had significantly higher beta 2m:HLA-ABC ratios than did the cells from other types of B-cell malignancy. Although leukaemic B cells with a demonstrable non HLA-ABC-associated beta 2m component expressed detectable levels of CD1c, and insignificant levels of CD1a and CD1b, the antigen density was insufficient to account for the excess beta 2m. In vitro stimulation of leukaemic B cells by phorbol ester substantially increased the expression of HLA-ABC and CD1c, but also accentuated further the difference between the expression of these molecules and that of beta 2m. There was no detectable beta 2m other than that associated with HLA-ABC and CD1 on the surface of malignant T cells by contrast. Our findings strongly support the existence, at certain stages of leukaemic B-cell differentiation, of an additional beta 2m component(s) other than that associated with HLA-ABC and CD1.
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PMID:The MHC class I associated beta 2-microglobulin (beta 2m) light chain is expressed in a molar excess over HLA-ABC and CD1 on the membrane of leukaemic B cells but not leukaemic T cells: evidence for further beta 2m-associated molecules. 171 10

Morphology, phenotype, and enzyme activity of highly enriched (80%) unlabeled human epidermal Langerhans cells (LC) have been studied, with emphasis on changes during a short-term culture of three days in vitro. All freshly isolated LC contained Birbeck granules and expressed high levels of CD1a, CD1c, and MHC class II molecules HLA-DR, -DP, and -DQ. They have a weak to moderate expression of RFD1, C3biR, Fc gamma R, p 150/95, MHC class I molecules HLA-ABC, and of the adhesion molecules LFA-3 and ICAM-1, whereas no expression of LFA-1 and several monocyte/macrophage markers were detected. Human LC undergo profound changes during in vitro culture. Birbeck granules, C3biR, Fc gamma R, and p 150/95 were completely lost and the expression of CD1a and CD1c was markedly decreased or lost. Expression of molecules that have essential functions in antigen presentation remained present at the same level (MHC class II molecules and ICAM-1) or was markedly enhanced (LFA-3 and MHC class I). Highly remarkable was the dramatically enhanced expression of interdigitating cell marker RFD1. The monocyte/macrophage markers initially absent remained absent and the enzyme activity initially present (including ATPase and nonspecific esterase) remained present. In conclusion, the results in this report stress rapid alterations of human LC during in vitro culture, resulting in transformation into cells that have phenotypical characteristics of potent antigen presenting cells that resemble interdigitating cells.
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PMID:Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture. 240 65

Beta 2-microglobulin (beta 2m) forms the invariant light chain of the MHC-encoded HLA-ABC and the non-MHC-encoded CD1 molecules. While HLA-ABC (MHC Class I) molecules are virtually ubiquitous in tissue distribution, CD1 determinants by contrast are more restricted. We have assessed, by indirect immunoenzymeassay, the relative membrane densities of these molecules on malignant thymic and post-thymic T cells. It was found that the T cells of mature post-thymic proliferations expressed significantly more beta 2m-associated protein, predominantly HLA-ABC in nature, than thymic-ALL blasts. This parallels the situation found in normal peripheral T cells and thymocytes. In contrast to post-thymic T cells, thymic-ALL blasts showed considerable case to case variation with respect to non-HLA-associated beta 2m and, of particular interest, not all of this excess beta 2m could be accounted for by CD1a. We therefore conclude that other beta 2m-containing molecules may be expressed on thymic-ALL blasts and possibly also on post-thymic leukaemic T cells. In addition, it was found that T cells from CD4+ cases of post-thymic proliferations expressed more beta 2m-associated determinants than other T cells, whether of either normal or malignant origin, and that certain post-thymic malignancies express significantly increased levels of beta 2m-associated protein relative to normal peripheral T-cells. This is in direct contrast to the situation seen in many solid malignancies.
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PMID:MHC class I and class I-like gene product expression by malignant T cells: relationships between CD1a, HLA-ABC and beta 2-microglobulin. 246 92

Beta 2-microglobulin (beta 2m) constitutes the 12 kD light chain of the MHC-encoded 43-kD glycoprotein HLA-ABC molecules, which are expressed on most nucleated cells. The T6 (CD1a) antigen is expressed on thymocytes in reciprocal manner to HLA-ABC, having a similar structure to the HLA-ABC molecule. We have determined the expression of beta 2m, HLA-ABC and the T6 antigen on the cell-surface of CD1a+ and CD1a- thymocytes (defined by NA1/34 expression), and have shown that despite immunophenotypic differences between these two stages of thymic maturation, the quantity of beta 2m-associated molecules expressed was not significantly different. The nature of the heavy (alpha) chain associated with beta 2m, however, differed since HLA-ABC had largely replaced T6 on the surface of CD1a- thymocytes. We also determined the expression of beta 2m and HLA-ABC on the surface of peripheral blood CD4+ and CD8+ T-cells, and showed that the CD8+ population expressed higher levels of these antigens than CD4+ T-cells, with no detectable excess beta 2m over HLA-ABC for either subpopulation. In addition, thymocytes expressed fewer beta 2m-associated determinants than peripheral blood T-cells. These results indicate an increase in the expression of beta 2m-associated molecules with differentiation from thymic to peripheral T-cell, with a further increase in such molecules expressed on the CD8+ compared to the CD4+ peripheral T-cell subpopulation.
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PMID:Expression of MHC class I and class I-like gene products on the cell membrane of mature and immature T cells. 305 69

The diagnosis of post-transfusion graft-versus-host disease (GVHD) in early period is critical for the prognosis of the patients. Exanthema and fever are the earliest symptom of the post-transfusion GVHD and usually precede the disturbance of the liver and bone marrow. Snap-frozen, cryostat-sectioned specimens from the lesional and perilesional skin were labeled by monoclonal antibodies against HLA-ABC, HLA- DR, ICAM-1, CD1a and CD8. The reaction was visualized by indirect immunofluorescence. Graft-versus-host reaction (GVHR) was immunopathologically characterized by extensive expression of HLA-DR and ICAM-1 in the epidermal keratinocytes, exocytosis of CD8 positive cytotoxic T-cell and the reduction or disappearance of CD1a expression by epidermal dendritic cells. The other GVHRs such as erythema exudativum multiforme (EEM), fixed drug eruption, toxic epidermal necrolysis (TEN) and lichen planus could not be separated. Our protocol of the immunopathologic examination could be done quickly (within 3 hours) and provides more detailed and useful information for the diagnosis of GVHD in early period compared with conventional histopathology.
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PMID:[Differential diagnosis of post-transfusion graft-versus-host disease (GVHD) by rapid immunopathologic examination of the skin]. 930 Dec 87

Although interferon alpha (IFN-alpha) is able to induce haematological remission in 60-80% of patients with chronic myeloid leukaemia (CML) in early chronic phase, major cytogenetic remissions are only achievable in 30-40%. Recent clinical data suggest that the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to IFN-alpha therapy can significantly improve the cytogenetic response in some patients, although the mechanism remains unknown. We hypothesized that the combination of GM-CSF and IFN-alpha induces the differentiation of dendritic cells, which subsequently stimulates a specific anti-leukaemic response. Monocytes from CML patients were cultured in GM-CSF and interleukin (IL)-4 (GM/IL-4)or in GM-CSF and IFN-alpha (GM/IFN-alpha). After 7 d, the number of cells exhibiting typical antigen-presenting cell (APC) morphology was equal in both groups, and fluorescence in situ hybridization (FISH) analysis confirmed that the APCs generated with GM/IFN-alpha were of leukaemic origin. Phenotypically, both sets of APCs expressed typical surface markers; however, CD86, CD83, CD11c, HLA-ABC and HLA-DR expression was significantly higher in the GM/IFN-alpha APCs, whereas CD1a expression was significantly lower. In mixed lymphocyte reactions (MLR), GM/IFN-alpha APCs stimulated the proliferation of allogeneic T cells significantly better than GM/IL-4 APCs. However, both groups of APCs stimulated autologous T-cell proliferation equally. Finally, we assessed the ability of GM/IFN-alpha APCs to induce a leukaemia-specific cytotoxic T-cell response. Some samples generated cytotoxic T lymphocytes (CTLs) that specifically lysed bcr-abl-positive target cells. These data show that the combination of GM-CSF and IFN-alpha, when used in vitro, induces the differentiation of malignant APCs with potent T-cell stimulatory capacity. Although there is no in vivo evidence to support these findings, it is possible that, when administered to CML patients, GM-CSF in combination with IFN-alpha results in the generation of highly stimulatory leukaemic APCs.
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PMID:Interferon alpha in combination with GM-CSF induces the differentiation of leukaemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukaemic cytotoxic T-cell response from patients with chronic myeloid leukaemia. 1112 8

We tried to efficiently generate human dendritic cells (DCs) from CD34+ peripheral blood hematopoietic progenitor cells mobilized by high-dose chemotherapy and subsequent administration of granulocyte colony-stimulating factor, using a liquid suspension culture system. Among various combinations, the combination of c-kit ligand, flt-3 ligand, c-mpl ligand (TPO), and interleukin (IL)-4 most potently generated the number of CD1a+CD14- DCs in cultures containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha). The delayed addition of IL-4 on day 6 of culture gave rise to an additional increase in the yield of CD1a+CD14-DCs that were characterized by the expression of HLA-ABC, HLA-DR, CD80, CD86, and CD83. The majority of the sorted CD1a-CD14+ cells derived from 6-day culture of CD34+ cells gave rise to CD1a+CD14- DCs and CD1a-CD14+ macrophages on day 12 of culture in the presence and absence of IL-4, respectively. These findings suggest that IL-4 promotes the differentiation of CD1a- CD14+ cells derived from mobilized CD34+ peripheral blood hematopoietic progenitors to CD1a+ CD14- DCs. The majority of these DCs expressed CD68 but not the Langerhans-associated granule antigen, a finding that suggests they emerge through the monocyte differentiation pathway. The addition of TPO and IL-4 to cultures did not affect the potential of DCs to stimulate the primary allogeneic T-cell response. These findings demonstrated that the combination of c-kit ligand plus flt-3 ligand plus TPO with GM-CSF plus TNF-alpha, followed by IL-4, is useful for ex vivo generation of human DCs from mobilized CD34+ peripheral blood progenitors.
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PMID:Efficient ex vivo generation of human dendritic cells from mobilized CD34+ peripheral blood progenitors. 1172 65

Human immunodeficiency virus (HIV)-1 Nef protein is an essential modulator of AIDS pathogenesis and we have previously demonstrated that rNef enters uninfected human monocytes and induces T cells bystander activation, up-regulating IL-15 production. Since dendritic cells (DCs) play a central role in HIV-1 primary infection we investigated whether rNef affects DCs phenotypic and functional maturation in order to define its role in the immunopathogenesis of AIDS. We found that rNef up-regulates the expression on immature DCs of surface molecules known to be critical for their APC function. These molecules include CD1a, HLA-DR, CD40, CD83, CXCR4, and to a lower extent CD80 and CD86. On the other hand, rNef down-regulates surface expression of HLA-ABC and mannose receptor. The functional consequence of rNef treatment of immature DCs is a decrease in their endocytic and phagocytic activities and an increase in cytokine (IL-1beta, IL-12, IL-15, TNF-alpha) and chemokine (MIP-1alpha, MIP-1beta, IL-8) production as well as in their stimulatory capacity. These results indicate that rNef induces a coordinate series of phenotypic and functional changes promoting DC differentiation and making them more competent APCs. Indeed, Nef induces CD4(+) T cell bystander activation by a novel mechanism involving DCs, thus promoting virus dissemination.
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PMID:HIV-1 Nef induces dendritic cell differentiation: a possible mechanism of uninfected CD4(+) T cell activation. 1196 93

Two common features in human immunodeficiency virus infection and acquired immunodeficiency syndrome, rheumatoid arthritis, and hematologic malignancies including multiple myeloma are elevated serum levels of beta(2)-microglobulin (beta(2)M) and activation or inhibition of the immune system. We hypothesized that beta(2)M at high concentrations may have a negative impact on the immune system. In this study, we examined the effects of beta(2)M on monocyte-derived dendritic cells (MoDCs). The addition of beta(2)M (more than 10 microg/mL) to the cultures reduced cell yield, inhibited the up-regulation of surface expression of human histocompatibility leukocyte antigen (HLA)-ABC, CD1a, and CD80, diminished their ability to activate T cells, and compromised generation of the type-1 T-cell response induced in allogeneic mixed-lymphocyte reaction. Compared with control MoDCs, beta(2)M-treated cells produced more interleukin-6 (IL-6), IL-8, and IL-10. beta(2)M-treated cells expressed significantly fewer surface CD83, HLA-ABC, costimulatory molecules, and adhesion molecules and were less potent at stimulating allospecific T cells after an additional 48-hour culture in the presence of tumor necrosis factor-alpha and IL-1beta. During cell culture, beta(2)M down-regulated the expression of phosphorylated mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), and mitogen-induced extracellular kinase (MEK), inhibited nuclear factor-kappaB (NF-kappaB), and activated signal transducer and activator of transcription-3 (STAT3) in treated cells, all of which are involved in cell differentiation and proliferation. Thus, our study demonstrates that beta(2)M at high concentrations retards the generation of MoDCs, which may involve down-regulation of major histocompatibility complex class I molecules, inactivation of Raf/MEK/ERK cascade and NF-kappaB, and activation of STAT3, and it merits further study to elucidate the underlying mechanisms.
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PMID:Beta 2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. 1253 97

Downregulation of major histocompatibility complex (MHC) class I, MHC-II, and intercellular adhesion molecule 1 (ICAM-1) expression in infected cell lines allows some viruses to escape host immunity. In skin lesions of varicella zoster virus (VZV), MHC-II transcripts were demonstrated in keratinocytes around vesicles, but not in VZV-infected cells. Whether other immunoevasive mechanisms are present during herpes zoster (HZ) is not yet elucidated. The aim of the study was to disclose the temporal immunohistochemical expression of immune escape mechanisms during HZ. Sequential skin biopsies were performed in 5 HZ patients. VZV IE63, CD1a, CD3, CD4, CD8, CD56, CD68, L1, HLA-DR, HLA-ABC, interleukin (IL)-6, IL-10, interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), and ICAM-1 expressions were assessed on frozen sections using immunohistochemistry. Controls consisted of normal skin, herpes simplex virus (HSV) skin infections, and other distinct bullous skin diseases. HLA-DR and ICAM-1 expressions were not observed in VZV- and HSV-infected keratinocytes, contrasting with their upregulation in the surrounding epidermis and inside nonviral blisters. However, HLA-ABC expressions were not inhibited in VZV-infected keratinocytes. Furthermore, the CD4/CD8 ratio remained unmodified during the infection evolution, and this ratio was variable among patients. Increased IFNgamma, TNFalpha, and IL-6 expressions were present, but IL-10 expression only increased in later stages. In contrast to in vitro MHC-I and MHC-II downregulation, VZV infection is related to MHC-II but not MHC-I expression on infected keratinocytes. The absence of ICAM-1 expression on infected keratinocytes may reduce their antigen presentation capacities to LFA-1 ligand-bearing T cells. This may represent another VZV-associated immune escape mechanism. Increased IFNgamma, TNFalpha, and IL-6 expressions suggest a TH1 profile.
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PMID:Absence of intercellular adhesion molecule 1 expression in varicella zoster virus-infected keratinocytes during herpes zoster: another immune evasion strategy? 1472 20


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