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Michael B. Brenner - One of the best experts on this subject based on the ideXlab platform.
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CD1 antigen presentation how it works
Nature Reviews Immunology, 2007Co-Authors: Duarte C. Barral, Michael B. BrennerAbstract:The classic concept of self-non-self discrimination by the immune system focused on the recognition of fragments from proteins presented by classical MHC molecules. However, the discovery of MHC-class-I-like CD1 antigen-presentation molecules now explains how the immune system also recognizes the abundant and diverse universe of lipid-containing antigens. The CD1 molecules bind and present amphipathic lipid antigens for recognition by T-cell receptors. Here, we outline the recent advances in our understanding of how the processes of CD1 assembly, trafficking, lipid-antigen binding and T-cell activation are achieved and the new insights into how lipid antigens differentially elicit CD1-restricted innate and adaptive T-cell responses.
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CD1 antigen presentation and t cell function
Annual Review of Immunology, 2004Co-Authors: Manfred Brigl, Michael B. BrennerAbstract:▪ Abstract 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 TCRα chains, self-lipid reactivity, and rapid effector responses empower a subset of CD1d-restr...
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fine specificity of tcr complementarity determining region residues and lipid antigen hydrophilic moieties in the recognition of a CD1 lipid complex
Journal of Immunology, 2002Co-Authors: Ethan P Grant, Samuel M. Behar, Gurdyal S. Besra, Steven A. Porcelli, Evan M Beckman, Stephen T Furlong, Massimo Degano, Daphney Frederique, Ian A Wilson, Michael B. BrennerAbstract:alphabeta TCR can recognize peptides presented by MHC molecules or lipids and glycolipids presented by CD1 proteins. Whereas the structural basis for peptide/MHC recognition is now clearly understood, it is not known how the TCR can interact with such disparate molecules as lipids. Recently, we demonstrated that the alphabeta TCR confers specificity for both the lipid Ag and CD1 isoform restriction, indicating that the TCR is likely to recognize a lipid/CD1 complex. We hypothesized that lipids may bind to CD1 via their hydrophobic alkyl and acyl chains, exposing the hydrophilic sugar, phosphate, and other polar functions for interaction with the TCR complementarity-determining regions (CDRs). To test this model, we mutated the residues in the CDR3 region of the DN1 TCR beta-chain that were predicted to project between the CD1b alpha helices in a model of the TCR/CD1 complex. In addition, we tested the requirement for the negatively charged and polar functions of mycolic acid for Ag recognition. Our findings indicate that the CDR loops of the TCR form the Ag recognition domain of CD1-restricted TCRs and suggest that the hydrophilic domains of a lipid Ag can form a combinatorial epitope recognized by the TCR.
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conservation of a CD1 multigene family in the guinea pig
Journal of Immunology, 1999Co-Authors: Christopher C Dascher, Samuel M. Behar, Steven A. Porcelli, Kenji Hiromatsu, Jerome Naylor, Pamela P Brauer, Kara A Brown, James R Storey, Ernest S Kawasaki, Michael B. BrennerAbstract:CD1 is a family of cell-surface molecules capable of presenting microbial lipid Ags to specific T cells. Here we describe the CD1 gene family of the guinea pig (Cavia porcellus). Eight distinct cDNA clones corresponding to CD1 transcripts were isolated from a guinea pig thymocyte cDNA library and completely sequenced. The guinea pig CD1 proteins predicted by translation of the cDNAs included four that can be classified as homologues of human CD1b, three that were homologues of human CD1c, and a single CD1e homologue. These guinea pig CD1 protein sequences contain conserved amino acid residues and hydrophobic domains within the putative Ag binding pocket. A mAb specific for human CD1b cross-reacted with multiple guinea pig CD1 isoforms, thus allowing direct analysis of the structure and expression of at least a subset of guinea pig CD1 proteins. Cell-surface expression of CD1 was detected on cortical thymocytes, dermal dendritic cells in the skin, follicular dendritic cells of lymph nodes, and in the B cell regions within the lymph nodes and spleen. CD1 proteins were also detected on a subset of PBMCs consistent with expression on circulating B cells. This distribution of CD1 staining in guinea pig tissues was thus similar to that seen in other mammals. These data provide the foundation for the development of the guinea pig as an animal model to study the in vivo function of CD1.
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recognition of a lipid antigen by CD1 restricted αβ t cells
Nature, 1994Co-Authors: Evan M Beckman, Samuel M. Behar, Steven A. Porcelli, Craig T Morita, Stephen T Furlong, Michael B. BrennerAbstract:MAJOR histocompatibility complex (MHC) class I and class II molecules bind immunogenic peptides and present them to lymphocytes bearing the αβ T-cell antigen receptor (TCR)1–4. An analogous antigen-presenting function also has been proposed for the non-MHC-encoded CD1 molecules5, a family of non-polymorphic, β2-microglobulin-associated glycoproteins5–8 expressed on most professional antigen-presenting cells9–11. In support of this hypothesis, CD1 molecules are recognized by selected CD4−CD8− αβ or γδ8TCR+ T-cell clones12–14, and we have recently shown that CD1 molecules restrict the recognition of foreign microbial antigens by αβTGR+ T cells10. But the substantial structural divergence of CD1 from MHC class I and class II molecules7, raises the possibility that the antigens presented by the CD1 system may differ fundamentally from those presented by MHC-encoded molecules. Here we report that a purified CDlb-restricted antigen of Mycobacterium tuberculosis presented to αβTCR+ T cells is mycolic acid, a family of α-branched, β-hydroxy, long-chain fatty acids found in mycobacteria15,16. This example of non-protein microbial antigen recognition suggests that αβTCR+ T cells recognize a broader range of antigens than previously appreciated and that at least one member of the CD1 family has evolved the ability to present lipid antigens.
Steven A. Porcelli - One of the best experts on this subject based on the ideXlab platform.
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Transcription of individual CD1 genes by bovine APCs.
2015Co-Authors: Thi Kim Anh Nguyen, Steven A. Porcelli, Peter Reinink, Chema El Messlaki, Altan Ercan, Ildiko Van RhijnAbstract:A Cells from PBMC (top panel), pseudoafferent lymph (middle panel), and prescapular lymph node (lower panel) were sorted based on expression of the Ig light chain (IL-A59), and CD1 (SBU-T6). The cDNA synthesized from the sorted cell populations was subjected to CD1 gene-specific PCR (B). C The CD1 expression of immature DCs, derived in vitro by treatment of monocytes with GM-CSF and IL-4, was confirmed and cDNA derived from the DCs, as well as cloned transcript as positive control template (Control), was subjected to CD1 gene-specific PCR.
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fine specificity of tcr complementarity determining region residues and lipid antigen hydrophilic moieties in the recognition of a CD1 lipid complex
Journal of Immunology, 2002Co-Authors: Ethan P Grant, Samuel M. Behar, Gurdyal S. Besra, Steven A. Porcelli, Evan M Beckman, Stephen T Furlong, Massimo Degano, Daphney Frederique, Ian A Wilson, Michael B. BrennerAbstract:alphabeta TCR can recognize peptides presented by MHC molecules or lipids and glycolipids presented by CD1 proteins. Whereas the structural basis for peptide/MHC recognition is now clearly understood, it is not known how the TCR can interact with such disparate molecules as lipids. Recently, we demonstrated that the alphabeta TCR confers specificity for both the lipid Ag and CD1 isoform restriction, indicating that the TCR is likely to recognize a lipid/CD1 complex. We hypothesized that lipids may bind to CD1 via their hydrophobic alkyl and acyl chains, exposing the hydrophilic sugar, phosphate, and other polar functions for interaction with the TCR complementarity-determining regions (CDRs). To test this model, we mutated the residues in the CDR3 region of the DN1 TCR beta-chain that were predicted to project between the CD1b alpha helices in a model of the TCR/CD1 complex. In addition, we tested the requirement for the negatively charged and polar functions of mycolic acid for Ag recognition. Our findings indicate that the CDR loops of the TCR form the Ag recognition domain of CD1-restricted TCRs and suggest that the hydrophilic domains of a lipid Ag can form a combinatorial epitope recognized by the TCR.
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conservation of a CD1 multigene family in the guinea pig
Journal of Immunology, 1999Co-Authors: Christopher C Dascher, Samuel M. Behar, Steven A. Porcelli, Kenji Hiromatsu, Jerome Naylor, Pamela P Brauer, Kara A Brown, James R Storey, Ernest S Kawasaki, Michael B. BrennerAbstract:CD1 is a family of cell-surface molecules capable of presenting microbial lipid Ags to specific T cells. Here we describe the CD1 gene family of the guinea pig (Cavia porcellus). Eight distinct cDNA clones corresponding to CD1 transcripts were isolated from a guinea pig thymocyte cDNA library and completely sequenced. The guinea pig CD1 proteins predicted by translation of the cDNAs included four that can be classified as homologues of human CD1b, three that were homologues of human CD1c, and a single CD1e homologue. These guinea pig CD1 protein sequences contain conserved amino acid residues and hydrophobic domains within the putative Ag binding pocket. A mAb specific for human CD1b cross-reacted with multiple guinea pig CD1 isoforms, thus allowing direct analysis of the structure and expression of at least a subset of guinea pig CD1 proteins. Cell-surface expression of CD1 was detected on cortical thymocytes, dermal dendritic cells in the skin, follicular dendritic cells of lymph nodes, and in the B cell regions within the lymph nodes and spleen. CD1 proteins were also detected on a subset of PBMCs consistent with expression on circulating B cells. This distribution of CD1 staining in guinea pig tissues was thus similar to that seen in other mammals. These data provide the foundation for the development of the guinea pig as an animal model to study the in vivo function of CD1.
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CD1 expression in human atherosclerosis a potential mechanism for t cell activation by foam cells
American Journal of Pathology, 1999Co-Authors: Agustin Melian, Peter Libby, Galina K Sukhova, Yongjian Geng, Steven A. PorcelliAbstract:Atherosclerotic plaques are chronic inflammatory lesions composed of dysfunctional endothelium, smooth muscle cells, lipid-laden macrophages, and T lymphocytes. This study analyzed atherosclerotic tissue specimens for expression of CD1 molecules, a family of cell surface proteins that present lipid antigens to T cells, and examined the possibility that CD1+ lipid-laden macrophages might present antigen to T cells. Immunohistochemical studies using a panel of specific monoclonal antibodies demonstrated expression of each of the four previously characterized human CD1 proteins (CD1a, -b, -c, and -d) in atherosclerotic plaques. Expression of CD1 was not observed in normal arterial specimens and appeared to be restricted to the CD68+ lipid-laden foam cells of atherosclerotic lesions. CD1 molecules colocalized in areas of the arterial wall that also contained abundant T lymphocytes, suggesting potential interactions between CD1+ cells and plaque-infiltrating lymphocytes in situ. Using CD1-expressing foam cells derived from macrophages in vitro, we demonstrated the ability of such cells to present lipid antigens to CD1 restricted T cells. Given the abundant T cells, CD1+ macrophages, and lipid accumulation in atherosclerotic plaques, we propose a potential role for lipid antigen presentation by CD1 proteins in the generation of the inflammatory component of these lesions.
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CD1 expression by dendritic cells in human leprosy lesions correlation with effective host immunity
Journal of Immunology, 1999Co-Authors: Peter A Sieling, Robert L Modlin, D Jullien, Monica Dahlem, Thomas F Tedder, Thomas H Rea, Steven A. PorcelliAbstract:A potential role for the CD1 family of lipid Ag-presenting molecules in antimicrobial immunity in vivo was investigated in human leprosy skin lesions. Strong induction of three CD1 proteins (CD1a, -b, and -c) was observed in dermal granulomas in biopsy samples of involved skin from patients with the tuberculoid form of leprosy or with reversal reactions, which represent clinical patterns of disease associated with active cellular immunity to Mycobacterium leprae. In contrast, lesions from patients with the lepromatous form of the disease who lack effective cell-mediated immunity to the pathogen did not show induction of CD1 proteins. Thus, expression of CD1 correlated directly with effective immunity to M. leprae, as assessed by the clinical course of infection. CD1a, -b, and -c could be induced to similar levels on monocytes from the blood of either tuberculoid or lepromatous leprosy patients. This suggested that the absence of expression in lepromatous lesions was most likely due to local factors at the site of infection as opposed to a primary defect of the CD1 system itself. The majority of cells expressing CD1 in leprosy lesions were identified as a population of CD83+ dendritic cells. Initial in vitro studies of the Ag-presenting function of CD1+CD83+ monocyte-derived dendritic cells showed that such cells were highly efficient APCs for CD1-restricted T cells. These results indicate that the CD1 system can be up-regulated in human infectious diseases in vivo, and may play a role in augmenting host defense against microbial pathogens.
Samuel M. Behar - One of the best experts on this subject based on the ideXlab platform.
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The role of group 1 and group 2 CD1-restricted T cells in microbial immunity.
Microbes and Infection, 2005Co-Authors: Markus Sköld, Samuel M. BeharAbstract:Group 1 and group 2 CD1 present both self and microbial lipid antigens to T cells. While group 1 CD1-restricted T cells are known for their ability to recognize mycobacterial glycolipid antigens, group 2 CD1-restricted T cells are recognized as regulatory T cells that can influence the outcome of innate and adaptive immune responses. The evidence that these T cells contribute to host defense against infectious diseases is reviewed.
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fine specificity of tcr complementarity determining region residues and lipid antigen hydrophilic moieties in the recognition of a CD1 lipid complex
Journal of Immunology, 2002Co-Authors: Ethan P Grant, Samuel M. Behar, Gurdyal S. Besra, Steven A. Porcelli, Evan M Beckman, Stephen T Furlong, Massimo Degano, Daphney Frederique, Ian A Wilson, Michael B. BrennerAbstract:alphabeta TCR can recognize peptides presented by MHC molecules or lipids and glycolipids presented by CD1 proteins. Whereas the structural basis for peptide/MHC recognition is now clearly understood, it is not known how the TCR can interact with such disparate molecules as lipids. Recently, we demonstrated that the alphabeta TCR confers specificity for both the lipid Ag and CD1 isoform restriction, indicating that the TCR is likely to recognize a lipid/CD1 complex. We hypothesized that lipids may bind to CD1 via their hydrophobic alkyl and acyl chains, exposing the hydrophilic sugar, phosphate, and other polar functions for interaction with the TCR complementarity-determining regions (CDRs). To test this model, we mutated the residues in the CDR3 region of the DN1 TCR beta-chain that were predicted to project between the CD1b alpha helices in a model of the TCR/CD1 complex. In addition, we tested the requirement for the negatively charged and polar functions of mycolic acid for Ag recognition. Our findings indicate that the CDR loops of the TCR form the Ag recognition domain of CD1-restricted TCRs and suggest that the hydrophilic domains of a lipid Ag can form a combinatorial epitope recognized by the TCR.
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regulation of CD1 function and nk1 1 t cell selection and maturation by cathepsin s
Immunity, 2001Co-Authors: Richard J. Riese, Jose A. Villadangos, Guo-ping Shi, Daniel B. Stetson, Christoph Driessen, Ching-liang Chu, Yuri N. Naumov, Anamaria Lennondumenil, Samuel M. BeharAbstract:NK1.1(+) T cells develop and function through interactions with cell surface CD1 complexes. In I-A(b) mice lacking the invariant chain (Ii) processing enzyme, cathepsin S, NK1.1(+) T cell selection and function are impaired. In vitro, thymic dendritic cells (DCs) from cathepsin S(-/-) mice exhibit defective presentation of the CD1-restricted antigen, alpha-galactosylceramide (alpha-GalCer). CD1 dysfunction is secondary to defective trafficking of CD1, which colocalizes with Ii fragments and accumulates within endocytic compartments of cathepsin S(-/-) DCs. I-A(k), cathepsin S(-/-) mice do not accumulate class II-associated Ii fragments and accordingly do not display CD1 abnormalities. Thus, function of CD1 is critically linked to processing of Ii, revealing MHC class II haplotype and cathepsin S activity as regulators of NK T cells.
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conservation of a CD1 multigene family in the guinea pig
Journal of Immunology, 1999Co-Authors: Christopher C Dascher, Samuel M. Behar, Steven A. Porcelli, Kenji Hiromatsu, Jerome Naylor, Pamela P Brauer, Kara A Brown, James R Storey, Ernest S Kawasaki, Michael B. BrennerAbstract:CD1 is a family of cell-surface molecules capable of presenting microbial lipid Ags to specific T cells. Here we describe the CD1 gene family of the guinea pig (Cavia porcellus). Eight distinct cDNA clones corresponding to CD1 transcripts were isolated from a guinea pig thymocyte cDNA library and completely sequenced. The guinea pig CD1 proteins predicted by translation of the cDNAs included four that can be classified as homologues of human CD1b, three that were homologues of human CD1c, and a single CD1e homologue. These guinea pig CD1 protein sequences contain conserved amino acid residues and hydrophobic domains within the putative Ag binding pocket. A mAb specific for human CD1b cross-reacted with multiple guinea pig CD1 isoforms, thus allowing direct analysis of the structure and expression of at least a subset of guinea pig CD1 proteins. Cell-surface expression of CD1 was detected on cortical thymocytes, dermal dendritic cells in the skin, follicular dendritic cells of lymph nodes, and in the B cell regions within the lymph nodes and spleen. CD1 proteins were also detected on a subset of PBMCs consistent with expression on circulating B cells. This distribution of CD1 staining in guinea pig tissues was thus similar to that seen in other mammals. These data provide the foundation for the development of the guinea pig as an animal model to study the in vivo function of CD1.
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recognition of a lipid antigen by CD1 restricted αβ t cells
Nature, 1994Co-Authors: Evan M Beckman, Samuel M. Behar, Steven A. Porcelli, Craig T Morita, Stephen T Furlong, Michael B. BrennerAbstract:MAJOR histocompatibility complex (MHC) class I and class II molecules bind immunogenic peptides and present them to lymphocytes bearing the αβ T-cell antigen receptor (TCR)1–4. An analogous antigen-presenting function also has been proposed for the non-MHC-encoded CD1 molecules5, a family of non-polymorphic, β2-microglobulin-associated glycoproteins5–8 expressed on most professional antigen-presenting cells9–11. In support of this hypothesis, CD1 molecules are recognized by selected CD4−CD8− αβ or γδ8TCR+ T-cell clones12–14, and we have recently shown that CD1 molecules restrict the recognition of foreign microbial antigens by αβTGR+ T cells10. But the substantial structural divergence of CD1 from MHC class I and class II molecules7, raises the possibility that the antigens presented by the CD1 system may differ fundamentally from those presented by MHC-encoded molecules. Here we report that a purified CDlb-restricted antigen of Mycobacterium tuberculosis presented to αβTCR+ T cells is mycolic acid, a family of α-branched, β-hydroxy, long-chain fatty acids found in mycobacteria15,16. This example of non-protein microbial antigen recognition suggests that αβTCR+ T cells recognize a broader range of antigens than previously appreciated and that at least one member of the CD1 family has evolved the ability to present lipid antigens.
Kimitaka Sagawa - One of the best experts on this subject based on the ideXlab platform.
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epitope mapping of CD1a CD1b and CD1c antigens in human skin differential localization on langerhans cells keratinocytes and basement membrane zone
Journal of Investigative Dermatology, 1992Co-Authors: Masutaka Furue, Margit Nindl, Katsura Kawabe, Koichiro Nakamura, Yasumasa Ishibashi, Kimitaka SagawaAbstract:CD1 antigens are classified into at least three groups, CDla, CDlb, and CDlc. In order to delineate the localization of epitopes of CD1 antigens in human skin, we examined the irnrnunoreactivity of fourteen different CD1 antibodies (seven CDla, five CDlb, and two CDlc antibodies). The epitopes for CDla, CDlb, and CDlc are differentially localized on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in normal human skin.
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epitopes for CD1a CD1b and CD1c antigens are differentially mapped on langerhans cells dermal dendritic cells keratinocytes and basement membrane zone in human skin
Journal of The American Academy of Dermatology, 1992Co-Authors: Masutaka Furue, Margit Nindl, Katsura Kawabe, Koichiro Nakamura, Yasumasa Ishibashi, Kimitaka SagawaAbstract:Background: CD1 antigens are classified serologically into at least three groups, CD1a, CD1b, and CD1c, and many kinds of monoclonal antibodies are available for each subgroup of CD1 antigens. CD1a, CD1b, and CD1c antigens have been shown to be selectively and differentially expressed on epidermal Langerhans cells and dermal dendritic cells in normal human skin. Objective: The objective was to further delineate the localization of epitopes of CD1 antigens in human skin. Methods: We examined the immunoreactivity of 14 different CD1 antibodies (seven CD1a, five CD1b, and two CD1c antibodies) with the immunoperoxidase technique. We also studied the reactivity of NU-T2 (CD1b) antibody by immunogold electron microscopy. Results: The epitopes for CD1a, CD1b, and CD1c antigens were differentially mapped on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in human skin. Conclusion: These CD1 antibodies may be useful to analyze the phenotypic alteration of immune and nonimmune cells in various skin diseases.
Robert L Modlin - One of the best experts on this subject based on the ideXlab platform.
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CD1 expression by dendritic cells in human leprosy lesions correlation with effective host immunity
Journal of Immunology, 1999Co-Authors: Peter A Sieling, Robert L Modlin, D Jullien, Monica Dahlem, Thomas F Tedder, Thomas H Rea, Steven A. PorcelliAbstract:A potential role for the CD1 family of lipid Ag-presenting molecules in antimicrobial immunity in vivo was investigated in human leprosy skin lesions. Strong induction of three CD1 proteins (CD1a, -b, and -c) was observed in dermal granulomas in biopsy samples of involved skin from patients with the tuberculoid form of leprosy or with reversal reactions, which represent clinical patterns of disease associated with active cellular immunity to Mycobacterium leprae. In contrast, lesions from patients with the lepromatous form of the disease who lack effective cell-mediated immunity to the pathogen did not show induction of CD1 proteins. Thus, expression of CD1 correlated directly with effective immunity to M. leprae, as assessed by the clinical course of infection. CD1a, -b, and -c could be induced to similar levels on monocytes from the blood of either tuberculoid or lepromatous leprosy patients. This suggested that the absence of expression in lepromatous lesions was most likely due to local factors at the site of infection as opposed to a primary defect of the CD1 system itself. The majority of cells expressing CD1 in leprosy lesions were identified as a population of CD83+ dendritic cells. Initial in vitro studies of the Ag-presenting function of CD1+CD83+ monocyte-derived dendritic cells showed that such cells were highly efficient APCs for CD1-restricted T cells. These results indicate that the CD1 system can be up-regulated in human infectious diseases in vivo, and may play a role in augmenting host defense against microbial pathogens.
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the CD1 system antigen presenting molecules for t cell recognition of lipids and glycolipids
Annual Review of Immunology, 1999Co-Authors: Steven A. Porcelli, Robert L ModlinAbstract:▪ Abstract Recent studies have identified the CD1 family of proteins as novel antigen-presenting molecules encoded by genes located outside of the major histocompatibility complex. CD1 proteins are conserved in all mammalian species so far examined and are prominently expressed on cells involved in antigen presentation, which suggests a role in activation of cell-mediated immunity. This has now been confirmed by functional studies demonstrating the ability of CD1 proteins to restrict the antigen-specific responses of T cells in humans and mice. Identification of naturally occurring antigens presented by CD1 has revealed the surprising finding that these are predominantly a variety of foreign lipids and glycolipids, including several found prominently in the cell walls and membranes of pathogenic mycobacteria. Structural, biochemical, and biophysical studies support the view that CD1 proteins bind the hydrophobic alkyl portions of these antigens directly and position the polar or hydrophilic head groups of...
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down regulation of CD1 on antigen presenting cells by infection with mycobacterium tuberculosis
Journal of Immunology, 1998Co-Authors: Steffen Stenger, Kayvan Niazi, Robert L ModlinAbstract:Intracellular pathogens have developed efficient evasion strategies to survive the defenses of the host immune system. In this study, we describe a new escape mechanism utilized by Mycobacterium tuberculosis that involves the down-regulation of the Ag-presenting molecule CD1 from the cell surface of CD1+ APCs. The loss of CD1 from the cell surface is associated with a complete inhibition of the ability of the infected cells to present Ag to CD1-restricted T cells. The down-regulation of Ag-presenting molecules on CD1+ APC by infection with M. tuberculosis is unique for CD1, since the expression of the classical Ag-presenting molecules MHC class I and MHC class II is not influenced. Our data show that efficient down-regulation of CD1 requires infection of the cells with live mycobacteria, since heat killing of the bacteria completely abrogates the effect. The observed down-regulation is not due to the secretion of cytokines or other host- or pathogen-derived factors. Investigation of upstream events responsible for the down-regulation of CD1 revealed that infection with live M. tuberculosis decreased the steady state CD1-mRNA levels. This study introduces a novel evasion mechanism of M. tuberculosis that could contribute to persistence of intracellular infection by avoiding immune recognition.