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)

Recent evidence has established that non-MHC-encoded molecules of the CD1 family mediate MHC-independent pathways for antigen presentation and T cell activation. Human group 1 CD1 molecules (CD1a, CD1b, CD1c) are expressed mainly on professional antigen-presenting cells, and mediate presentation of microbial lipid and glycolipid antigens to T cells. These group 1 CD1 molecules differentially sample distinct endocytic compartments that may contain different sets of lipid antigens derived from intracellular microbes, and activate antigen-specific T cells. These T cells lyse infected antigen-presenting cells and secrete Th1 cytokines, such as interferon- gamma, and granulysin, a potent antimicrobial protein, and thus can control microbial infection. Reactivity to CD1a, b, and c molecules in the absence of foreign antigen has also been detected in T cells bearing alphabeta and gammadelta TCRs. These T cells may recognize self-lipid antigens and are considered to be autoreactive. In particular, the main tissue subset of gammadelta T cells (V delta 1(+)subset) show prominent reactivity to CD1c, and produce interferon- gamma and granulysin. These CD1c directly reactive T cells may mediate immunity against microbial infection even before antigen-specific T cells differentiate and expand. Together, human CD1a, b and c molecules elicit T cell-dependent immunity to the universe of foreign and self-lipid antigens in both innate and acquired immunity settings.
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PMID:T lymphocyte recognition of human group 1 CD1 molecules: implications for innate and acquired immunity. 1114 56

Four human CD1 isoforms (CD1a, -b,-c and -d) are now known to be antigen presenting molecules with the unique ability to present lipid antigens to T cells. CD1b and CD1d are found in acidic, late endocytic compartments, whereas CD1a and CD1c molecules accumulate at the plasma membrane and in early endosomes. Consistent with their differences in intracellular localization, most studies show antigen presentation by CD1b/CD1d to be dependent on endosomal acidification while CD1a/CD1c mediated antigen presentation is not. Taken together, recent advances in the analysis of CD1 molecules reinforce the hypothesis that the different CD1 isoforms are specialized to survey the lipid content of distinct intracellular compartments. This may help to explain the duplication and diversification of CD1 genes in humans and other mammalian species.
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PMID:Diversification of CD1 proteins: sampling the lipid content of different cellular compartments. 1114 57

Canine oral papillomavirus (COPV) infection is used in vaccine development against mucosal papillomaviruses. The predictable, spontaneous regression of the papillomas makes this an attractive system for analysis of cellular immunity. Immunohistochemical analysis of the timing and phenotype of immune cell infiltration revealed a marked influx of leukocytes during wart regression, including abundant CD4+ and CD8+ cells, with CD4+ cells being most numerous. Comparison of these findings, and those of immunohistochemistry using TCRalphabeta-, TCRgammadelta-, CD1a-, CD1c-, CD11a-, CD11b-, CD11c-, CD18-, CD21-, and CD49d-specific monoclonal antibodies, with previously published work in the human, ox, and rabbit models revealed important differences between these systems. Unlike bovine papillomavirus lesions, those of COPV do not have a significant gamma/delta T-cell infiltrate. Furthermore, COPV lesions had numerous CD4+ cells, unlike cottontail rabbit papillomavirus lesions. The lymphocyte infiltrate in the dog resembled that in human papillomavirus lesions, indicating that COPV is an appropriate model for human papillomavirus immunity.
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PMID:Regression of canine oral papillomas is associated with infiltration of CD4+ and CD8+ lymphocytes. 1131 59

CD1 proteins are a family of cell surface molecules that present lipid antigens to T cells. We investigated skin dendritic cells and monocyte-derived dendritic cells for expression of CD1 molecules using a panel of 10 different monoclonal antibodies focusing on the recently described CD1d molecule. By immunohistochemical analysis, CD1d expression in normal human skin was restricted to dendritic appearing cells in the papillary dermis mainly located in a perivascular localization. Langerhans cells did not show detectable CD1d expression in situ. Epidermal/dermal cell suspensions analyzed by flow cytometry demonstrated distinct subpopulations of HLA-DR positive dermal dendritic cells expressing CD1a, CD1b, and CD1c. CD1d was expressed on HLA-DRbright dermal antigen-presenting cells in dermal suspensions (16% +/- 3.6%), as well as on highly enriched dermal dendritic cells migrating out of skin explants (60.5% +/- 8.0%). Migrated mature dermal dendritic cells coexpressed CD83 and CD1d. Western blot analysis on microdissected skin sections revealed the presence of a 50-55 kDa CD1d molecule in dermis, suggesting that CD1d is highly glycosylated in skin. Both immature and mature monocyte-derived dendritic cells cultured in autologous plasma expressed CD1d molecules. In contrast, culture in fetal bovine serum downregulated CD1d expression. In conclusion, antigen-presenting cells in skin express different sets of CD1 molecules including CD1d and might play a role in lipid antigen presentation in various skin diseases. Differential expression of CD1 molecules depending on culture conditions might have an impact on clinical applications of dendritic cells for immunotherapy.
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PMID:Cd1d is expressed on dermal dendritic cells and monocyte-derived dendritic cells. 1156 62

Pulmonary Langerhans cell Histiocytosis is a rare granulomatous disease affecting both sexes, with greater incidence in the second and third decades of life; smoking appears to be the most important risk factor. Its etiology is unknown, although there are data indicating an uncontrolled immune response as possible cause, sustained by the Langerhans cells, antigen presenting cells for T lymphocytes, and their accumulation in the distal bronchioles; these cells express on their surface the CD1a and CD1c antigens, and the B7 molecule, essential for activating quiescent T lymphocytes. In its evolution the granuloma is characterized by the progressive reduction in the LC number, with the increase of fibrosis, surrounding and destroying the bronchiolar lumen; the remaining of the lumen, or the traction exerted by fibrous tissue on the adjacent alveolar spaces leads to the cyst development. Vascular involvement occurs frequently, and may explain the onset of pulmonary hypertension in advanced cases of the disease. The disease may be asymptomatic, or it may present with aspecific respiratory signs and symptoms, and has characteristic radiological findings, being included in the group of cysticaerial parenchymal alterations. The diagnosis could be suggested by the finding of a number of LC in BAL greater than 5%. Different therapies have been proposed, but it seems that the most important measure is smoking cessation.
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PMID:Pulmonary Langerhans cell Histiocytosis. 1158 96

Five CD1 molecules are expressed in humans and it is unclear whether they have specialized or redundant functions. We found that sulfatide is a promiscuous CD1-binding ligand and have isolated T cell clones that are specific for sulfatide and restricted by distinct CD1 molecules. These clones have been used to compare the capacity of different CD1 to present the same glycolipid, to induce effector functions, and to form persistent immunogenic complexes. CD1a, CD1b, and CD1c molecules similarly load sulfatide on the cell surface without processing, and prime Th1 and Th2 responses. Stimulation by sulfatide-loaded CD1a persists much longer than that by CD1b and CD1c in living cells. Use of recombinant soluble CD1a confirmed the prolonged capacity to stimulate T cells. Moreover, other glycosphingolipids bind to all CD1, which suggests the presence of additional promiscuous ligands. Thus, group I CD1 molecules present an overlapping set of self-glycolipids, even though they are quite divergent from an evolutionary point of view.
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PMID:Presentation of the same glycolipid by different CD1 molecules. 1195 92

CD1 molecules are cell-surface glycoproteins with strong structural similarities to major histocompatibility complex (MHC) class I molecules, and studies in humans and mice have demonstrated that CD1 proteins perform the unique role of presenting lipid antigens to T lymphocytes. Our previous studies have shown that guinea-pigs, unlike the muroid rodents, have an extended family of group 1 CD1 genes. In the current study, we raised monoclonal anibodies (mAbs) against guinea-pig CD1 proteins and generated transfected cell lines expressing individual members of the guinea-pig CD1 family. Our results indicated that multiple members of the guinea-pig CD1 family, including members that are homologous to the human CD1b and CD1c proteins, are expressed at the protein level in transfected cells and in specialized antigen-presenting cells such as monocyte-derived dendritic cells. In addition, CD1 proteins, especially guinea-pig CD1b3, were expressed on a large number of B cells in the guinea-pig, and CD1 expression appeared to be regulated by B-cell maturation or differentiation. Interestingly, three different patterns of intracellular localization were observed for the various guinea-pig CD1 isoforms, a finding that is reminiscent of the distinct patterns of intracellular localization that have been previously demonstrated for human CD1a, CD1b and CD1c. Taken together, these results provide further evidence for substantial similarities between the guinea-pig and human CD1 systems, thus supporting the possibility that the guinea-pig may offer significant advantages as an animal model for the study of the in vivo role of CD1 proteins in infectious and autoimmune diseases.
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PMID:Characterization of guinea-pig group 1 CD1 proteins. 1204 45

Upon exposure to Ag and inflammatory stimuli, dendritic cells (DCs) undergo a series of dynamic cellular events, referred to as DC maturation, that involve facilitated peptide Ag loading onto MHC class II molecules and their subsequent transport to the cell surface. Besides MHC molecules, human DCs prominently express molecules of the CD1 family (CD1a, -b, -c, and -d) and mediate CD1-dependent presentation of lipid and glycolipid Ags to T cells, but the impact of DC maturation upon CD1 trafficking and Ag presentation is unknown. Using monocyte-derived immature DCs and those stimulated with TNF-alpha for maturation, we observed that none of the CD1 isoforms underwent changes in intracellular trafficking that mimicked MHC class II molecules during DC maturation. In contrast to the striking increase in surface expression of MHC class II on mature DCs, the surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). In addition, unlike MHC class II, DC maturation-associated transport from lysosomes to the plasma membrane was not readily detected for CD1b despite the fact that both molecules were prominently expressed in the same MIIC lysosomal compartments before maturation. Consistent with this, DCs efficiently presented CD1b-restricted lipid Ags to specific T cells similarly in immature and mature DCs. Thus, DC maturation-independent pathways for lipid Ag presentation by CD1 may play a crucial role in host defense, even before DCs are able to induce maximum activation of peptide Ag-specific T cells.
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PMID:CD1 molecules efficiently present antigen in immature dendritic cells and traffic independently of MHC class II during dendritic cell maturation. 1239 Nov 86

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.
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PMID:CD1 antigen presentation and infectious disease. 1253 Mar 26

Langerhans cells are a critical component of skin immunity, capable of capturing protein antigens in the epidermis and presenting them to specific T cells in the context of major histocompatibility complex class II molecules. Recently, a major histocompatibility complex independent pathway of lipid antigen presentation has been identified and is mediated by molecules of the CD1 family (CD1a, CD1b, CD1c, and CD1d). Because Langerhans cells are professional antigen-presenting cells and express CD1a molecules prominently, we hypothesized that Langerhans cells might play a role in T cell responses directed against not only peptide antigens but also lipid antigens. Here, we show that freshly isolated immature Langerhans cells as well as mature Langerhans cells that have migrated from the epidermis are efficient in presenting foreign microbial lipid antigens to specific T cells whereas dermal dendritic cells express much less CD1a molecules and function inefficiently. Further, we found that Langerhans cells migrating from epidermal sheets that were exposed to microbial lipid antigens expressed lipid-antigen-loaded CD1a molecules on the cell surface, resulting in activation of specific T cells. These results underscore an outstanding ability of Langerhans cells to mediate CD1a-dependent lipid antigen presentation. Thus, Langerhans-cell-mediated skin immunity may involve T cell recognition of both peptide and lipid antigens.
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PMID:Epidermal Langerhans cells efficiently mediate CD1a-dependent presentation of microbial lipid antigens to T cells. 1292 10


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