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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Antigen-presenting (APC), suppressor T-cell-inducing macrophages infiltrate both human and murine epidermis after ultraviolet radiation (UVR) exposure. To determine their derivation, we prepared epidermal cell and dermal cell suspensions from human keratome biopsy specimens obtained from nonexposed skin and from UVB-irradiated sites (3 d after four times the minimal erythema dose). Simultaneous triple-marker flow cytometric analysis established the extended phenotype of macrophages infiltrating sunburned human epidermis (CD1a- CD1c- CD11b+ CD11c+ CD36+ Fc gamma RII+ DR+). This then enabled us to track dermal cells of this phenotype after UVR in relation to the heterogeneous DR+ populations in normal dermis. By both in situ immunohistology and cell suspension flow cytometry, UVR induced an expansion of bone marrow-derived DR+ cells in the perivasculature and sub-basement membrane zone of the papillary dermis. Despite an overall expansion of DR+ cells, the CD1a+ CD1c+ CD36- DR+ Langerhans-cell-like dendritic APC subset of dermal DR+ cells was depleted (p < 0.05), indicating that UVR-induced epidermal Langerhans cell loss (from 95% to 7% of DR+ epidermal cells) is not accounted for by Langerhans cell accumulation in the dermis. By contrast, UVR exposure induced a selective expansion of the dermal macrophage subset, which is phenotypically identical to the monocytic/macrophagic APCs that appear in the epidermis after UV injury (p < 0.01). Cell cycle analysis (to determine whether this expansion was accounted for entirely by infiltration) revealed no increase in the percentage of DR+ CD36+ UVR-exposed dermal cells in S/G2/M phase; however, the expanded DR+ CD36+ subset continued its already substantial level of proliferation unabated. Therefore, epidermal macrophages derive not only from transcapillary migration, but also from in situ proliferation of a dermal precursor. Taken together, these findings show that UVR creates an epidermal and dermal APC milieu which is dominated by monocytic/macrophagic cells, through depletion of cells of dentritic APC phenotype, and concomitant selective dermal expansion of a CD1a- CD1c- CD11b+ CD36+ Fc gamma RII+ DR+ (monocyte/macrophage) population.
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PMID:In human dermis, ultraviolet radiation induces expansion of a CD36+ CD11b+ CD1- macrophage subset by infiltration and proliferation; CD1+ Langerhans-like dendritic antigen-presenting cells are concomitantly depleted. 749 Apr 72

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

In human epidermis, expression of CD1a is confined to Langerhans cells (LC), whereas CD1c expression has been observed in dendritic cells of the dermis, as well as the epidermis. In transfected fibroblasts, expression of CD1c at the cell surface appears to exclude expression of either CD1b or CD1a, despite continued transcription of the latter genes. In order to determine whether this mechanism might be operative in human skin, we have compared the expression of CD1a and CD1c on the surface of dermal and epidermal dendritic cells to their expression at the level of mRNA using a combination of dual-label immunofluorescence microscopy, northern blot hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR). By both immunofluorescence and Northern blotting, CD1c expression was observed in both dermal and epidermal cells, whereas expression of CD1a was confined largely to the epidermis. Moreover, as shown by immunomagnetic bead selection and RT-PCR, CD1a and CD1c were both expressed on epidermal LC, but were absent from other epidermal cell types. These results argue against cell surface exclusion as a mechanism for selective expression of CD1c in human dermis.
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PMID:CD1 gene expression in human skin. 751 Sep 98

Human CD1 genes are a family of five non-polymorphic genes that, although homologous to both class I and II major histocompatibility complex genes, map to chromosome 1. Only three of the antigens, CD1a, -b, and -c, have been clustered with monoclonal antibodies. They are noncovalently associated with beta 2-microglobulin and may function as nonclassical antigen-presenting molecules. Here we analyze their expression in mouse myeloma transfectants and human thymocytes and find mRNA splicing complexity. This manifests itself as incomplete splicing, alternative splicing, utilization of cryptic splice sites, and the generation of alternative reading frames. In the case of CD1A transfectants, we demonstrate that the major protein product is secreted and show by amino acid sequence analysis that this is derived from an unspliced transcript. A second major CD1a component appears to be retained intracellularly. The production of alternatively spliced transcripts in the thymus is not a feature of all CD1 genes. Although in the case of CD1A only the transcript encoding the cell surface CD1a isoform is found, CD1C and -E produce complex intrathymic splicing patterns. The CD1C transcripts predict the expression of a secreted CD1c isoform in the human thymus, which we detect in CD1C transfectant culture supernatants. CD1 gene expression is thus characterized by considerable splicing complexity, and the difference between the splicing patterns found in different environments suggests that this is tissue specific.
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PMID:Alternative splicing generates secretory isoforms of human CD1. 751 59

The cDNA encoding the rat homologue of CD1 was isolated and the complete nucleotide sequence was determined. It contained an open reading frame of 1008 bp that was capable of encoding a polypeptide with 336 amino acids composed of hydrophobic leader and transmembrane sequences, three extracellular domains, and 5' and 3' untranslated sequences. Comparison of the amino acid sequence of rat CD1 with those of other species revealed that it showed the highest similarity to mouse CD1, which belongs to the CD1D class of the CD1 system and is distinct from the classic CD1 class including CD1a, CD1b, and CD1c expressed primarily on human thymocytes and some dendritic cells. Widespread transcription of rat CD1 was readily detected by Northern blot analysis in nonlymphoid organs, including the liver, kidney, and heart, as well as in lymphoid organs, including the thymus, lymph node, and spleen. Intestinal expression was also demonstrated by the more sensitive reverse transcription-PCR method. Immunoprecipitation with a rabbit anti-rat CD1 Ab showed that rat CD1 was expressed on the cell surface as a beta 2-microglobulin-associated heterodimer. Southern blot analysis of inbred rat strains suggested that rat CD1 shows limited polymorphism and that only one CD1 gene is detectable in the F344 rat genome. These results provide evidence for the conservation of CD1D class through mammalian evolution and an apparent lack of the classic CD1 class genes in rodents. Functional similarity of rodent CD1 is implied.
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PMID:Structural analysis of the rat homologue of CD1. Evidence for evolutionary conservation of the CD1D class and widespread transcription by rat cells. 751 72

Epidermal Langerhans cell heterogeneity is poorly understood with regard to phenotypic characteristics, such as the expression of human leukocyte antigen (HLA)-DR, integrin, and Fc receptor molecules, as well as functional characteristics, such as the ability to process and present antigens or produce cytokines during various phases of immigration and maturation. Technical limitations of Langerhans cell number have limited functional assays on putative Langerhans cell subsets in in vivo epidermis. Therefore, we used flow cytometry for simultaneous phenotypic and functional assessment at the single-cell level within the Langerhans cell population. Freshly isolated human epidermal cell suspensions were stained with a battery of monoclonal antibodies, including anti-HLA-DR, -CD1a, -CD1c, -CD11c, -Fc gamma RII, and -Fc epsilon RI. Two distinct Langerhans cell subsets were identified by their different levels of HLA-DR expression. The DRHi subset expressed higher amounts of CD11c and exhibited greater cytoplasmic complexity and higher baseline calcium than the DRLo subset (p < or = 0.03 for each). Some subjects also expressed high levels of Fc epsilon RI in the DRHi, CD11cHi subset. To determine whether these phenotypic subsets may exhibit differential signal-transduction functional properties, Langerhans cells were partially enriched over Ficoll-Hypaque and their cytosolic mobilization after the addition of ionomycin was analyzed using the calcium indicator, indo-1, in conjunction with quantitative analysis of HLA-DR expression. By this real-time flow cytometric analysis, a new subpopulation was revealed within the DRLo Langerhans cell subset. This subset increased its cytosolic calcium concentration much more than the other two subsets (change in indo-1 blue:violet emission ratio of 37.33 +/- 2.34 in the Hi Flux DRLo subset versus 13.23 +/- 0.29 in the Lo Flux DRLo subset, and versus 7.6 +/- 2.99 in the Lo Flux DRHi subset). These data indicate that functional, as well as phenotypic, subsets of Langerhans cells exist within normal human epidermis. Their responses to physiologic stimuli may relate to maturational stage or the level of in vivo activation.
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PMID:Differential responsiveness of Langerhans cell subsets of varying phenotypic states in normal human epidermis. 752 45

Recent immunohistochemical investigations of thyroid carcinomas have revealed that dense infiltration by dendritic cells (DCs) is correlated with a favorable prognosis. The present study was done to clarify the frequency and characteristics of DC infiltration in thyroid carcinomas, and also cytokines associated with DC maturation and migration. Compared with follicular carcinomas, papillary carcinomas contained significantly higher numbers of DCs, interleukin (IL)-1 alpha- and tumor necrosis factor (TNF)-alpha-positive cells, and cells positive for two TNF-alpha receptors (p60 and p80). The centers of cancer nodules had large numbers of CD1a- and CD1c-positive DCs suggesting that they were Langerhans cells, whereas the periphery of cancer nodules and inflamed surrounding thyroid tissues had numerous CD1b-, L-M2- and X-12-positive DCs suggesting that they were interdigitating cells, as well as many CD1a- and CD1c-positive DCs. Neoplastic cells of papillary carcinomas were more frequently reactive with antibodies against IL-1 alpha and TNF-alpha than those of follicular carcinomas, and a good correlation between their immunoreactivity and the frequency of DCs was found. These data suggest that cytokines such as IL-1 alpha and TNF-alpha released from carcinoma cells and cells in the cancer stroma may regulate the infiltration and maturation of dendritic/Langerhans cells, and that this process may be better preserved in papillary than in follicular carcinomas.
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PMID:Immunohistochemical analysis of dendritic/Langerhans cells in thyroid carcinomas. 757 48

Human V gamma 2V delta 2+ T cells recognize mycobacterial nonpeptide antigens, such as isopentenyl pyrophosphate, and their synthetic analogs, such as monoethyl phosphate, through a TCR-dependent process. Here, we examine the presentation of these antigens. V gamma 2V delta 2+ T cells recognized secreted prenyl pyrophosphate antigens in the absence of other accessory cells but, under such conditions, required T cell-T cell contact. Recognition required neither the expression of classical MHC class I, MHC class II, or CD1a, CD1b, and CD1c molecules, nor MHC class I or class II peptide loading pathways. Fixed accessory cells also presented the prenyl pyrophosphate antigens to gamma delta T cells. Thus, in contrast with the presentation of conventional peptide antigens, protein antigens, and superantigens to alpha beta T cells, prenyl pyrophosphate antigens are presented to gamma delta T cells through a novel extracellular pathway that does not require antigen uptake, antigen processing, or MHC class I or class II expression. This pathway allows for the rapid recognition of bacteria by gamma delta T cells and suggests that gamma delta T cells play a role in the early response to bacterial infection.
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PMID:Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells. 758 40


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