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)

We have studied the effects of phorbol-dibutyrate (PBu2), a protein kinase C (PKC) activator, on the proliferation of peripheral human T cells and thymocyte subpopulations selected by treatment with monoclonal antibodies and complement: pre-thymocytes (CD1a-CD3-CD4-CD8-), cortical thymocytes (CD3-, class I- antigens) and medullary thymocytes (enriched as CD1a- cells). PBu2 induces a dose-dependent proliferative response in human peripheral blood T cells at concentrations greater than 6 ng/ml, this proliferation being mediated by the autocrine interleukin 2 (IL2)/IL2 receptor (IL2R) pathway. Pre-thymocytes respond to PBu2 in a way similar to T cells, being able to secrete IL2 in significant amounts and express the p55 chain of IL2R. On the other hand, cortical thymocytes are not induced to proliferate after PKC activation and neither expression of the p55 chain of IL2R nor IL2 secretion is observed. Human medullary thymocytes, phenotypically identical to peripheral blood T cells, show no proliferation in response to PBu2 at any concentration tested unless IL2 is supplied to the cultures. The activation of PKC induces the expression of IL2R in these cells, but not IL2 secretion. The implications of PKC activation in thymic maturation, the role of IL2 and the relevance of the differences between medullary thymocytes and peripheral blood T cells are discussed.
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PMID:Proliferative responses induced by the activation of protein kinase C during the development of human T lymphocytes. 199 83

We describe the clinical, ultrastructural, and immunophenotypical characteristics of four cases of an unusual type of T cell leukemia. Clinical features included high WBC, ranging from 26-148 x 10(9)/liter, bone marrow infiltration, splenomegaly, and lymphadenopathy. Skin involvement was not documented at presentation, but it was seen as a terminal event in one patient with a pattern of dermal lymphocytic infiltration different from that usually seen in Sezary syndrome. By ultrastructural analysis, the circulating lymphoid cells were indistinguishable from small Sezary cells in two cases, resembled large Sezary cells in one case, and consisted of a mixture of small Sezary cells and prolymphocytes in the remaining case. The cells from all cases had a mature T cell phenotype, TdT-, CD1a-, CD2+/-, CD3+, CD5+. In addition, the cells were either CD8+, CD4- or CD8+, CD4+ or CD4-, CD8-; and, in only one case, the findings were similar to those of Sezary syndrome cells: CD4+, CD8-, CD7-, BE-2+. In the latter case, serological and immunological assays were positive for HTLV-I while these were negative in two other patients investigated. The features of these patients suggest that Sezary cell leukemia is a distinct clinico-pathological entity although the alternative diagnosis of adult T cell leukemia/lymphoma could not be excluded in the HTLV-I+ case. Sezary cell leukemia appears to be resistant to current chemotherapy regimens and is associated with an aggressive clinical course and short survival.
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PMID:Sezary cell-like leukemia: a distinct type of mature T cell malignancy. 236 82

Human cluster-of-differentiation 1 (CD1) is a family of cell surface glycoproteins of unknown function expressed on immature thymocytes, epidermal Langerhans cells and a subset of B lymphocytes. Three homologous proteins, CD1a, b and c, have been defined serologically, and the CD1 gene locus on human chromosome 1 contains five potential CD1 genes. Analysis of the predicted amino-acid sequences of CD1 molecules reveals a low but significant level of homology to major histocompatibility complex (MHC) class I and class II molecules, and, like MHC class I molecules, CD1 molecules are associated non-covalently with beta 2-microglobulin. These structural similarities to known antigen-presenting molecules, together with the expression of CD1 on cells capable of antigen presentation, suggest a role for CD1 molecules in antigen recognition by T cells. Here we demonstrate the specific recognition of CD1a by a CD4-CD8- alpha beta T-cell receptor (TCR) expressing cytolytic T lymphocyte (CTL) line and the specific recognition of CD1c by a CD4-CD8- gamma delta TCR CTL line. The interaction of CD1-specific CTLs with CD1+ target cells appeared to involve the CD3-TCR complex, and did not show evidence of MHC restriction. These results suggest that for a subset of T cells, CD1 molecules serve a function analogous to that of MHC class I and II molecules.
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PMID:Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes. 247 5

Normal human oral (check) mucosa was studied to discover whether the oral cavity resembles the Mucosal Immune System (MIS) or the Skin Immune System (SIS). Immunophenotypes of lymphocyte subsets and Langerhans cells (LC) with their exact locations in the epithelium and papillary layer of the normal buccal mucosa were determined and compared with data of normal human skin. In a double staining procedure, the distribution of T-lymphocytes in relation to blood and lymph vessels was determined. Immunophenotyping of LC was done with a CD1a monoclonal antibody. In contrast to the skin, T-lymphocytes in buccal mucosa are not primarily perivascular in location. They are more or less randomly distributed on both sides of the basement membrane. The epithelium of the buccal mucosa contains about 37 times as many T-lymphocytes as the epidermis of normal skin. T-cell numbers in the papillary layer are more or less comparable. The CD4/CD8 ratios of about 1/2 in the epithelium of buccal mucosa and 1/4 in the skin indicates preferential presence of the CD8 subset in both sites, but the helper/inducer T-lymphocytes play a much greater role in the epithelium of the buccal mucosa when compared with skin. B-lymphocytes were not found in the epithelium and papillary layer of the buccal mucosa. Thus, immune response associated cells in buccal mucosa do not show the MIS pattern since B cells are absent. It has more in common with SIS but differences are also apparent. In the epithelium of the buccal mucosa the density of LC does not differ significantly from that of the skin, but the papillary layer of the buccal mucosa contains significantly fewer LC than the skin. As in the skin most of the LC of the buccal mucosa are found in the epithelium.
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PMID:Quantification and distribution of lymphocyte subsets and Langerhans cells in normal human oral mucosa and skin. 257 Jan 42

The CD1 gene family encodes at least three proteins: CD1a, CD1b, and CD1c, which are coexpressed on cortical thymocytes and a number of T cell leukemias. On thymocytes, CD1a forms noncovalent complexes with CD1b and CD1c, and a disulfide-linked heterodimer with CD8. This report describes the isolation and characterization of cDNA clones encoding the CD1a, CD1b, and CD1c Ag. Cotransfection of the cDNA was used to investigate the formation of intermolecular heterodimers by CD1a with other members of the CD1 gene family and with CD8. No intermolecular heterodimers were observed during transient expression in COS cells. However, an exclusion hierarchy was observed between members of the CD1 gene family when two or more members of the family were cotransfected into COS cells.
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PMID:Expression of cDNA clones encoding the thymocyte antigens CD1a, b, c demonstrates a hierarchy of exclusion in fibroblasts. 270 45

The first cluster of differentiation (CD1) defines at least three distinct human thymic cell-surface differentiation antigens-CD1a, CD1b, and CD1c. We looked for structural homology of the three CD1 heavy chains at their peptide level by two-dimensional peptide maps. We show here that the CD1a Mr 49,000 heavy chain and the CD1b Mr 45,000 heavy chain appear to be more homologous to each other than to the CD1c Mr 43,000 heavy chain and that only one tyrosil peptide is common to the three heavy chains. Study of the CD1 heavy chains from several individuals reveals a very limited polymorphism of these molecules. We also demonstrate here that CD1a or CD1a-like molecules and other CD1 molecules can form intermolecular complexes on the surface of normal thymus cells. Molecules that are structurally very similar to CD1a molecules are associated noncovalently either with CD1c molecules or with CD1b molecules, and only CD1a molecules can associate covalently with CD8 molecules. In contrast, we could not find these intermolecular complexes on the surface of leukemic T-cell lines in culture.
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PMID:Intermolecular complexes between three human CD1 molecules on normal thymus cells. 327 18

We looked at the surface expression of the three distinct human thymic cell surface differentiation antigens, CD1a, CD1b, and CD1c, that presently define the first cluster of differentiation (CD) on the cells from 34 patients with acute T cell malignancies. We also studied the expression of other T cell-restricted molecules, including the T cell receptors, on these cells. Our results confirm the extensive phenotypic heterogeneity of the cells from acute T cell malignancies, which contrast with the more limited phenotypic diversity of subacute or chronic T cell malignancies. Our study of normal children and fetal thymus cells shows that the extensive phenotypic heterogeneity of the malignant cells reflects the heterogeneity of the thymic subpopulations and shows that most of the phenotypes observed on malignant T cells have a normal counterpart, particularly in the fetal thymus. Moreover, we demonstrate that the CD1a molecules, which can form three different types of noncovalent intermolecular complexes on the surface of normal thymus cells, do not form any noncovalent intermolecular complexes on the surface of leukemic cells. We also show that CD1a molecules can form covalent intermolecular complexes with CD8 molecules on some but not all malignant cells.
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PMID:Analysis of CD1 molecules on thymus cells and leukemic T lymphoblasts identifies discrete phenotypes and reveals that CD1 intermolecular complexes are observed only on normal cells. 349 78

The human gut epithelium is a unique immunological compartment, containing substantial amounts of intra-epithelial lymphocytes (IEL) with unknown functions. In this study we show that distinct and unusual subpopulations of IEL are present at different levels of human intestine. IEL phenotypes in normal jejunum, ileum and colon were compared using immunoflow cytometry and immunohistochemistry. The expression of mRNA for recombination-activating gene-1 (RAG-1) in IEL from all three levels was compared using reverse-transcription polymerase chain reaction, and the morphology of IEL in situ was determined using immunoelectron microscopy. Surface marker profiles of isolated intestinal epithelial cells at all three levels were also investigated. On average the proportion of TCR gamma delta IEL was comparable in jejunum than ileum and colon and varied in phenotype with gut level. CD4-CD8-TCR alpha beta IEL dominated in colon but were absent in jejunum. CD8+ TCR alpha beta IEL were present at all levels but only in jejunum did they constitute the majority of all IEL. CD4+ TCR alpha beta IEL were present in similar frequencies at all levels of the gut. In general, the majority of IEL had an activated phenotype (CD45RO+, alpha E beta 7+). Furthermore, IEL exhibited phenotypes which are rare in peripheral blood. The thymocyte markers CD1a and CD1c as well as the NK cell marker CD56 were expressed on a fraction of TCR alpha beta and TCR gamma delta IEL. A small population of 'null' cells (CD45+ TCR/CD#-CD20-CD14-CD15- cells) was also present at equal proportions along the gut. Jejunal but not colonic IEL expressed RAG-1 mRNA suggesting that extrathymic T cell maturation occurs in the epithelium of small intestine. RAG-1 was expressed in CD2+TCR/CD3- and CD3+/TCR-IEL. Ultrastructurally, IEL often formed small clusters and intimate contacts with epithelial cells, suggesting cell cooperation within the epithelium. Some IEL had pseudopodium-like extensions penetrating the epithelial basement membrane suggesting transmigration. Epithelial cells in small intestine but not colon expressed heat shock protein 60 and HLA-DR. CD1a, CD1b and CD1c were not expressed on intestinal epithelial cells at any level. The distinct surface marker profiles of IEL and epithelial cells along small and large intestine suggest functional regional specialization and are compatible with the hypothesis that TCR alpha beta IEL participate in immune reactions to lumenal antigens while TCR gamma delta IEL perform surveillance of the epithelium.
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PMID:Intra-epithelial lymphocytes. Evidence for regional specialization and extrathymic T cell maturation in the human gut epithelium. 749 55

The expression of immune associated surface antigens of keratinocytes was studied in human papillomavirus (HPV) derived lesions in order to determine whether HPV types have a regulatory role in the pathogenesis of papillomas. A series of cutaneous and mucosal lesions were immunolabeled with monoclonal antibodies to the major histocompatibility complex class 1 (beta 2-microglobulin) and 2 (HLA-DR antigens), intercellular adhesion molecule (ICAM-1) and glycoprotein CD36 (OKM5) as well as CD1a (Langerhans cells), CD4, CD8 (T cells) and CD11a (LFA1 antigen). Testing for the presence of HPV was carried out by in situ hybridization with biotinylated probes for viral DNA detection and typing. We observed a drastic reduction or a loss of beta 2-microglobulin by keratinocytes from cutaneous lesions in correlation with the disappearance of Langerhans cells. Only mild alterations were observed in mucosal lesions. HLA-DR expressed by keratinocytes was only detected in condylomas and laryngeal papillomas and was usually associated with a dense inflammatory reaction. This HLA-DR expression may be correlated with an up-regulation of ICAM-1 and the presence of LFA1 positive leukocytes, mainly of CD8 phenotype, in the epithelium. CD36 was detected on differentiated keratinocytes of all lesions; its expression seems related to the proliferation state of the lesions and probably does not represent an immune marker. The different reactivity patterns observed in cutaneous and mucosal lesions may reflect: 1. different roles for mucosal and cutaneous HPV types in the induction of immunoregulatory surface antigens of keratinocytes, or 2. the changing nature of the cytokines released by mononuclear cells and infected keratinocytes in these lesions.
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PMID:Expression of immune associated surface antigens of keratinocytes in human papillomavirus-derived lesions. 750 44

The cell-surface expression of the MIC2 antigen defined by the monoclonal antibody 12E7 was investigated on human leukocytes in bone marrow (BM), thymus, and peripheral blood (PB) using multiparameter flow cytometry and cell sorting. In contrast to preceding reports, we found that the MIC2 antigen is not restricted to T cells and monocytes. We show that it is also expressed in the B cell and in the granulocytic lineage, the levels of expression being related to distinct maturational stages. CD34+ cells of BM were found to express the antigen at high levels. Along the granulocytic maturation pathway from CD34+CD33+ blasts to mature granulocytes, MIC2 densities appeared progressively reduced with a considerable decline at the myelocyte stage. In B lymphopoiesis, the earliest CD34+ CD10+ B-cell precursor (BCP) cells, further subdivided by expression of CD19, displayed the highest MIC2 density of BM leukocytes. All later BCP stages showed lower MIC2 expression levels, with a remarkable reduction concomitant with loss of the CD34 antigen at the CD10+CD20- surface mu-chain- stage, and a subsequent slight upregulation along with maturation to CD10-CD20high surface mu-chain+ BCPs. The brightest MIC2 expression of all cells tested was displayed by the most immature thymic T-lineage cells characterized by the antigenic profile CD34weakor- CD7++ surface CD3-CD1a(weak) CD4weak CD8-or weak. Common thymocytes stained slightly less intense with 12E7, whereas all subsequent stages of T-lineage cells in thymus, PB, or BM showed markedly reduced MIC2 levels. Mature peripheral CD4+ as well as CD8+ T cells displayed a bimodal distribution of MIC2. In the CD4+ population, the distinct MIC2 levels were related to the well-studied functional subdivision by differential expression of CD45 isoforms, the helper-inducer/memory subset showing higher MIC2 expression than helper-suppressor/naive CD4+ T cells. Similarly high MIC2 densities were found on CD16+ natural killer cells and on CD14+ monocytes, whereas mature peripheral B cells exhibited low or intermediate expression, and granulocytes exhibited no or only dim expression. These results document that the MIC2 antigen (1) is expressed on all leukocyte lineages; (2) is differentially expressed during T- and B-lymphoid, as well as granulocytic maturation; (3) shows highest expression in the most immature lymphocytic and granulocytic developmental stages; and (4) is also differentially expressed on functional T-cell subsets. We speculate that these observations imply a functional significance of MIC2 in the network of hematopoietic adhesion pathways.
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PMID:Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood. 750 50


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