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At least 19 recordsLinked to original sources
PubMed1991

Evolutionary origin and diversification of the mammalian CD1 antigen genes.

CD1 antigens are cell-surface glycoproteins which have a molecular structure which is similar (consisting of extracellular domains alpha 1, alpha 2, and alpha 3, a transmembrane portion, and a cytoplasmic tail) to that of class I MHC molecules. Phylogenetic analysis of mammalian CD1 DNA sequences revealed that these genes are more closely related to the class I major histocompatibility complex (MHC) than to the class II MHC and that mammalian genes are more closely related to avian class I MHC genes than they are to mammalian class I MHC genes. The CD1 genes form a multigene family with different numbers of genes in different species (five in human, eight in rabbit, and two in mouse). Known CD1 genes are grouped into the following three families, on the basis of evolutionary relationship: (1) the human HCD1B gene and a partial sequence from the domestic rabbit, (2) the human HCD1A and HCD1C genes, and (3) the human HCD1D and HCD1E genes plus the two mouse genes and a sequence from the cottontail rabbit. The alpha 1 and alpha 2 domains of CD1 are much less conserved at the amino acid level than are the corresponding domains of class I MHC molecules, but the alpha 3 domain of CD1 seems to be still more conserved than the well-conserved alpha 3 domain of class I MHC molecules. Furthermore, in the human CD1 gene family, interlocus exon exchange has homogenized alpha 3 domains of all CD1 genes except HCD1C.

Amino Acid Sequence↗
PubMed2005

CD1 assembly and the formation of CD1-antigen complexes.

The CD1 antigen presentation system presents lipid antigens to effector T cells, which have diverse roles in antimicrobial responses, antitumor immunity and in regulating the balance between tolerance and autoimmunity. The trafficking of CD1 molecules and lipid antigens facilitates their intersection and binding in specific intracellular compartments. Recent studies have now identified unexpected accessory molecules that are critical to CD1 assembly and lipid loading. The atomic structures of CD1-antigen complexes have defined both the orientation of polar headgroups between the alpha1 and alpha2 helices of CD1 and the manner in which distinct CD1 isoforms bind a range of lipids that have different lengths and numbers of hydrocarbon chains.

Animals↗
PubMed1997

Analysis of the requirement for beta 2-microglobulin for expression and formation of human CD1 antigens.

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.

Antibodies, Monoclonal↗
PubMed1988

[Langerhans cell: CD1 antigens and the Birbeck granule].

Langerhans cells are characterized by two types of markers: an ultrastructural marker, the Birbeck granule and different membrane markers: HLA-D antigens, T4 antigen, and some of the CD1 antigens. These antigens which are specific for the epidermal Langerhans cells, are not expressed by the other epidermal cells. Three CD1 antigens are biochemically defined on human thymocytes, they display a glycoprotein chain non covalently attached to beta-2-microglobulin. Only two of these glycoproteins: the T6 and M241 molecules have been detected on Langerhans cells. The presence of these CD1 antigens on Langerhans cells enhances their relationships to thymocytes, in contrast, Langerhans cells cannot be any more easily associated with the macrophage-monocyte lineage. The physiology of the ultrastructural marker is not well known. Its membrane origin has been experimentally proved since T6 antigen has been found closely associated to newly formed Birbeck granules.

Animals↗
PubMed2006

Synthesis of sulfated galactocerebrosides from an orthogonal beta-D-galactosylceramide scaffold for the study of CD1-antigen interactions.

CD1a protein binds sulfatide (3-O-sulfo-beta-D-galactosylceramide) to form an antigen complex that interacts with T cell receptors and activates T cells. To assess the role of the position of the sulfate in T cell activation, the synthesis of three beta-D-galactosylceramides, variously bearing a sulfate at position 2, 4, or 6 of galactose, has been planned and carried out. The compounds were synthesized by an orthogonal sulfation strategy from a common beta-D-galactosylceramide scaffold, which was in turn obtained through an efficient glycosylation reaction between a fully orthogonally protected galactosyl imidate and 3-O-benzoylazidosphingosine. Immunological evaluation of the three sulfated compounds in CD1a-mediated T cell activation, in comparison with natural sulfatide, provided evidence of the influence of the sulfate position in the recognition event between the antigen, the CD1 protein and the T cell receptor.

Antigens, CD1↗
PubMedDate not supplied

Analysis of CD1 molecules on haematological malignancies of myeloid and lymphoid origin. II. Intracellular detection of CD1 antigens.

The surface and cytoplasmic expression of CD1a molecules was analysed by indirect immunofluorescence (IIF) and dot blot assay (DBA) in a panel of 40 acute and chronic leukaemias. Thirty-two per cent of the samples were positive by IIF but, surprisingly, 72 per cent of the patients were positive by DBA, suggesting the intracellular presence of these molecules, CD1b and CD1c were also detected by DBA at similar percentages. Immunocytochemical staining of cytocentrifuge preparations confirmed the intracellular presence of CD1a, CD1b, and CD1c in leukaemic cells of pre-B, B, T, and non-lymphoid lineages.

Antigens, CD↗
PubMed1989

Expression of CD1 antigens by peripheral blood mononuclear cells from hepatitis B patients.

We have studied the expression of CD1 antigens on peripheral blood mononuclear cells (PBMC) from acute hepatitis B patients in order to analyse a possible role for CD1 antigens in hepatitis B virus (HBV) infection. Using immunofluorescence and the monoclonal antibodies which recognized CD1a, CD1b and CD1c molecules, we have shown that CD1 antigens were expressed on PBMC from acute hepatitis B patients but not from other acute and chronic liver disease. Dot blot analysis on nitrocellulose sheets of the lysates of the cells confirmed these observations. Cell fractionation and double-labelling experiments clearly demonstrated the CD1 antigens were expressed only on non-T cells. Furthermore, CD1 antigens were coexpressed with hepatitis B surface antigen (HBsAg) on the surface of Ig-positive cells. These results could indicate that CD1 expression may be associated with the lymphotropic effect of HBV.

Adolescent↗
PubMed1999

Amino-terminal sequencing of sheep CD1 antigens and identification of a sheep CD1D gene.

The anti-CD1 monoclonal antibodies IAH-CC14 and SBU-T6 were used to immunopurify CD1 antigens from sheep thymocytes. The amino-terminal sequence of IAH-CC14 yielded 13 amino acids, and 29 amino acids were obtained from the SBU-T6 antigen. The sequence of the IAH-CC14 antigen was 100% identical to the predicted sequence of the sheep CD1B clone, SCD1B-42. The 29 amino acid sequence of the SBU-T6 antigen did not match identically with the derived amino acid sequence of any of the previously reported sheep CD1 genes but had closest similarity to the derived sequence of human CD1E. Degenerate polymerase chain reaction primers based on this sequence identified a group 2 sheep CD1 gene. The predicted amino acid sequence of this gene shows that it is not identical to the SBU-T6 peptide, indicating that a different, CD1D-like gene was cloned.

Amino Acid Sequence↗
PubMed2003

CD1 antigen presentation and infectious disease.

Taken together, the data generated thus far strongly suggest that CD1 plays a role in the immune response against various infections (table 1). For obvious reasons, the data gathered thus far using model infection systems have focused primarily on the mouse and therefore only examine the role of CD1d. This leaves an important gap in our understanding of the CD1 antigen presentation pathway given the potential role of CD1a, CD1b and CD1c for contributing to antimicrobial immunity. The functional dichotomy between group 1 and group 2 CD1 isoforms obviously requires further analysis. However, we propose that the group 1 CD1 (CD1a, CD1b, CD1c) antigen presentation pathway is closer to the traditional adaptive immune response mechanisms with the capacity to present unique foreign antigens to specific T cells. This broadens the universe antigens that T cells can use to target pathogens and provides important antimicrobial effector mechanisms that may be critical for combating some types of infections. Lipid antigens may also provide a more effective means of targeting intracellular pathogens by T cells since CD1 is able to sample almost all of the intracellular reservoirs that are exploited by this class of pathogen and may provide an important component of the cytotoxic T cell response [80]. On the other hand, the group 2 CD1 protein (CD1d) may be more intermediate in terms of lying functionally between the innate and adaptive immune systems. The activation of CD1d-restricted T cells may, therefore, help bridge the temporal gap between the onset of innate immunity and the purely adaptive responses typified by the MHC-restricted T cells. Hence, the CD1d-restricted [table: see text] T cells are primed for rapid high-level cytokine release. In addition, the interaction of CD1d-restricted T cells with CD1d on DCs can trigger the release of IL-4 and GM-CSF to promote maturation of tissue-resident DC at the site of infection. The maturation of tissue DC would lead to migration of the activated DC to regional lymph nodes and initiation of MHC-restricted T cell responses. Subsequent IL-12 production by the DC in response to CD1d-mediated T cell stimulation could then drive IFN-gamma production by CD1d-restricted T cells and influence the polarization of the T cell response to infection. In addition, early bursts of IFN-gamma by CD1d-restricted T cells could also upregulate antimicrobial activity in macrophages and activate other important effector cells such as NK cells prior to MHC-restricted T cell responses. In the constant struggle between the microbial pathogen and its host, the evolutionary balance almost always favors the microbe. The rapid rate of evolution and adaptation of the microbe accounts for most of this advantage. Hence, it is not surprising that the host immune system has evolved a complex set of pathways, in addition to the MHC, that are able to recognize and target the unique molecular signatures of infectious microorganisms. The lipid antigens presented by CD1 add to this array and thus provide a further layer of immune defense to the host for combating pathogens.

Animals↗
PubMed2003

Intracellular pathways of CD1 antigen presentation.

Each of the human CD1 proteins takes a different route through secretory and endocytic compartments before finally arriving at the cell surface, where these proteins present glycolipid antigens to T cells. Recent studies have shown that adaptor-protein complexes and CD1-associated chaperones control not only CD1 trafficking, but also the development and activation of CD1-restricted T cells. This indicates that CD1 proteins, similar to MHC class I and II molecules, selectively acquire certain antigens in distinct cellular subcompartments. Here, we summarize evidence supporting the hypothesis that CD1 proteins use separate, but parallel, pathways to survey endosomal compartments differentially for lipid antigens.

Adaptor Proteins, Vesicular Transport↗
PubMed1988

Interleukin 1 induces CD1 antigen expression on human gingival epithelial cells.

The CD1 (T6) antigen is a highly specific marker for human Langerhans cells (LC). Previous studies have demonstrated that crude preparations containing murine interleukin-1 (IL-1) or a human epithelial cell-derived IL-1 inhibitor (ILS) modulate CD1 expression by LC in organ culture. This study examined the effect of organ-culture derived human IL-1, recombinant human IL-1, and purified ILS on CD1 expression in dispersed epithelial cell cultures. Both IL-1 preparations stimulated CD1 expression in whole and CD1-depleted cultures. The optimal dose level for this effect was 0.5 U/ml. Higher dose levels did not result in an increase in CD1 expression, implying that a limited pool of CD1 negative EC are induced to express CD1 by IL-1. Induction of CD1 expression on whole and depleted EC was abrogated by ILS. These results indicate that human IL-1 and an IL-1 inhibitor act in combination to modulate CD1 expression on Langerhans cells in the gingival epithelium.

Antibodies, Monoclonal↗
PubMed2004

CD1: antigen presentation and T cell function.

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.

Animals↗
PubMed1988

Sensitive and high resolution in situ hybridization to human chromosomes using biotin labelled probes: assignment of the human thymocyte CD1 antigen genes to chromosome 1.

A method for in situ hybridization originally developed for mapping genes in the nematode, Caenorhabditis elegans has been adapted for high resolution cytological mapping of genes in the human. The probe DNAs are labelled by incorporation of biotin dUTP and the site of hybridization detected by immunofluorescence. For the accurate assignment of the hybridization signal to chromosome bands, visualized by staining with Hoechst 33258, a heterologous ribosomal DNA probe is also included in the hybridization reaction. These rDNA signals are used as fiducial markers when aligning the two fluorescent images. We demonstrate the method by assignment of the human thymocyte CD1 antigen genes to human chromosome 1q22-23.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Associated expression of CD1 antigen and Fc receptor for IgE on epidermal Langerhans cells from patients with atopic dermatitis.

The presence of Fc receptors for IgE on epidermal Langerhans cells (LC) from patients with atopic dermatitis (AD) was demonstrated by three different types of experiments. Firstly, cell-bound IgE on LC was removed by acid elution and restored by highly purified human myeloma IgE (IgE kappa). Secondly, after pepsin digestion of cell-bound IgE the number of LC staining with anti-human light chain (kappa, lambda) antibodies significantly decreased in contrast to the number of LC staining with anti-human epsilon heavy chain antibody. Thirdly, LC formed rosettes with sheep red blood cells (SRBC) coated with IgE kappa. Epidermal LC from normal non-atopic controls, did not form rosettes with SRBC-IgE. The SRBC-IgE rosette formation could be inhibited by preincubation with IgE kappa and BB10 (MoAb directed against the Fc receptor for IgE on human eosinophils, platelets and macrophages), but also with human IgG, whereas the SRBC-IgG rosette formation could be inhibited neither by IgE kappa nor by BB10. Both the SRBC-IgE and the SRBC-IgG rosette formation could be inhibited by OKT6 (anti-CD1) antibody. The results of inhibition studies with OKT6 antibody on the reconstitution of IgE on epidermal LC after acid elution suggest an associated expression of the CD1 antigen and the Fc receptor for IgE.

Antigens, Differentiation↗
PubMed2006

CD1 antigen presentation by human dendritic cells as a target for herpes simplex virus immune evasion.

In contrast to MHC molecules, which present peptides, the CD1 molecules have been discovered to present lipid Ags to T cells. CD1-restricted T lymphocytes have been recently associated with resistance to virus infection. The mechanisms underlying activation of CD1-restricted T cells in the course of virus infection are not defined. In this study, we wanted to investigate the interaction of HSV with the antiviral CD1 Ag presentation system in human dendritic cells (DC). In response to low titers of HSV, the surface expression of CD1b and CD1d on human DC was up-regulated. These phenotypic changes enhanced the capacity of infected DC to stimulate proliferation of CD1-restricted T lymphocytes. High titers of HSV, however, lead to strong down-regulation of all surface CD1 molecules. This modulation of surface expression was associated with intracellular accumulation, colocalization with viral proteins, and disruption of the CD1 recycling machinery. Finally, even at low titers HSV interfered with the capacity of infected DC to stimulate the release of important cytokines by CD1d-restricted NKT cells. Thus, we demonstrate both the existence of a CD1 pathway allowing human DC to react to viral infection, as well as its blockage by a human herpesvirus.

Antigen Presentation↗
PubMed2003

Upregulation of group 1 CD1 antigen presenting molecules in guinea pigs with experimental autoimmune encephalomyelitis: an immunohistochemical study.

In humans, group 1 CD1 glycoproteins present foreign and self lipid and glycolipid antigens to T-cells. Homologues of these molecules are not found in mice or rats but are present in guinea pigs (GPs). We examined CD1 and MHC class II expression in the central nervous system (CNS) of GPs sensitized for experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. In normal GPs and the uninflamed CNS, low-level MHC class II (MHC II) immunoreactivity occurred on vascular elements, meningeal macrophages and parenchymal microglial cells, whereas immunoreactivity for CD1 was absent. In the inflamed CNS, the majority of infiltrating cells were MHC II+ and microglia showed increased expression. CD1 immunoreactivity was detected on astrocytes and subsets of inflammatory cells Including B cells and macrophages. Minimal CD1 and MHC II co-expression was noted on inflammatory cells or glia. We conclude that group 1 CD1 molecules are strongly upregulated in the inflamed CNS on subsets of cells distinct from the majority of MHC II bearing cells. The expression of CD1 proteins in such lesions broadens the potential repertoire of antigens recognized at these sites and highlights the value of the GP as a model for studies of the relevance of CD1 molecules in host defense and autoimmune diseases.

Age Factors↗
PubMed2005

Mycobacterium tuberculosis regulates CD1 antigen presentation pathways through TLR-2.

Mycobacterium tuberculosis remains a major pathogen of worldwide importance, which releases lipid Ags that are presented to human T cells during the course of tuberculosis infections. Here we report that cellular infection with live M. tuberculosis or exposure to mycobacterial cell wall products converted CD1- myeloid precursors into competent APCs that expressed group 1 CD1 proteins (CD1a, CD1b, and CD1c). The appearance of group 1 CD1 proteins at the surface of infected or activated cells occurred via transcriptional regulation, and new CD1 protein synthesis and was accompanied by down-regulation of CD1d transcripts and protein. Isolation of CD1-inducing factors from M. tuberculosis using normal phase chromatography, as well as the use of purified natural and synthetic compounds, showed that this process involved polar lipids that signaled through TLR-2, and we found that TLR-2 was necessary for the up-regulation of CD1 protein expression. Thus, mycobacterial cell wall lipids provide two distinct signals for the activation of lipid-reactive T cells: lipid Ags that activate T cell receptors and lipid adjuvants that activate APCs through TLR-2. These dual activation signals may represent a system for selectively promoting the presentation of exogenous foreign lipids by those myeloid APCs, which come into direct contact with pathogens.

Animals↗