DOCSLIB.ORG

Functional Expression Human Cd1d Cytoplasmic Tail Controls Its A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Functional Expression Human Cd1d Cytoplasmic Tail Controls Its A The Journal of Immunology A Threonine-Based Targeting Signal in the Human CD1d Cytoplasmic Tail Controls Its Functional Expression Jianyun Liu,* Daniel Shaji,* Sungyoo Cho,* Wenjun Du,† Jacquelyn Gervay-Hague,† and Randy R. Brutkiewicz* CD1d molecules are MHC class I-like molecules that present lipids to a unique subpopulation of T cells called NKT cells. The cytoplasmic tail of human CD1d possesses a tyrosine-based endosomal targeting motif (YXXZ). As such, these molecules traffic through the endocytic pathway, where it is believed that they are loaded with the antigenic lipid that stimulates NKT cells. In the current study, it was found that the T322 residue in the human CD1d tail is a major signal controlling transport to the cell surface and thus its functional expression. Mimicking the phosphorylation of this residue or removal of the entire cytoplasmic tail negates its ability to regulate CD1d trafficking, resulting in lysosomal targeting and degradation. These results demonstrate an important role of a heretofore unknown signal in the cytoplasmic tail of CD1d that may have relevance to other type I integral membrane proteins that traverse through the endocytic pathway. The Journal of Immunology, 2010, 184: 4973–4981. D1 molecules are nonpolymorphic transmembrane gly- lipids, including phosphatidylinositol and phosphatidylcholine, coproteins encodedby geneslocatedoutside theMHC locus generally cannot activate NKT cells. Instead, they likely play an C (1). There are five members of the CD1 family: CD1a, analogous role to the invariant chain-derived CLIP peptide for CD1b, CD1c, CD1d, and CD1e. Like MHC class I, all of the CD1 MHC II (4). Either before or after lipid loading, the CD1d H proteins consist of three extracellular domains (a1, a2, and a3), chain binds to b2m and then is transported to the Golgi. In the a transmembrane domain, and cytoplasmic tail. The CD1 a3do- Golgi, the glycans on CD1d are processed further before being mains are nonconvalently associated with b2-microglobulin (b2m), transported to the plasma membrane (12, 13). From the surface, forming a heterodimer soon after translation in the endoplasmic due to the YXXZ motif (where Y is tyrosine, X is any amino acid, reticulum (ER) (2, 3). Unlike MHC class I and class II molecules and Z is bulky hydrophobic residue) in its cytoplasmic tail, surface that present peptide Ags, CD1 molecules present lipids to T cells. CD1d is internalized and traffics through compartments of the The CD1d molecule presents lipid Ags mostly to a unique sub- endocytic pathway (5, 14). CD1d-mediated lipid Ag presentation population of T cells that express an invariant TCR a-chain and requires lipid exchange in late endocytic compartments and re- surface markers also present on NK cells (4). These are thus named expression on the cell surface to activate NKT cells (15, 16). invariant NKT cells. Activated NKT cells secrete both Th1 (e.g., Sphingolipid activator proteins, especially saposin B, may facilitate IFN-g and GM-CSF) and Th2 (e.g., IL-4) cytokines, playing im- lipid binding to CD1d (or other CD1 molecules) throughout the en- portant roles in both innate and adaptive immunity (5), including docytic pathway (17–20). Among the lipid Ags that activate NKT cells, antitumor, autoimmune, and antimicrobial responses (6–8). some are natural cellular ligands, such as isoglobotrihexosylceramide, Microsomal triglyceride transfer protein, a protein involved in whereas others are microbial lipids such as a-glucuronosylceramide lipoprotein assembly (9), has been reported to be important for from Sphingomonas (21–23). a-Galactosylceramide (a-GalCer), CD1d function in vivo. It is likely required for the loading of self- a glycolipid extracted from marine sponges, is recognized by invariant lipids into the hydrophobic groove formed by the a1 and a2 NKT cells in a CD1d-dependent manner (4, 24). domains of CD1d when synthesized in the ER (10, 11). These self- CD1d a type I transmembrane protein and its cytoplasmic tail contains at least one signal for endocytic trafficking (Supplemental Fig. 1). Both human and mouse CD1d cytoplasmic tails contain *Department of Microbiology and Immunology, Indiana University School of Med- icine, Indianapolis, IN 46202; and †Department of Chemistry, University of Califor- a YXXZ motif, which is believed to be a binding motif for the nia at Davis, Davis, CA 95616 adaptor protein (AP) 2m1 subunit and AP3, respectively (25). Received for publication May 7, 2009. Accepted for publication March 1, 2010. Destroying this motif causes the accumulation of both human and This work was supported by National Institutes of Health Grants R01 AI46455 and mouse CD1d on the cell surface (15, 26). Interestingly, the YXXZ P01 AI056097 (to R.R.B.) and National Science Foundation Grant CHE-0194682 (to motif is also required for CD1d downregulation caused by a mi- J.G.-H.). crobial infection, such as HIV and Chlamydia (13, 27, 28). The Address correspondence and reprint requests to Dr. Randy R. Brutkiewicz, Depart- lysine in the CD1d cytoplasmic tail is also believed to be im- ment of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, Building R2, Room 302, Indianapolis, IN 46202. E-mail address: portant, because the monoubiquitination of lysines can also [email protected] function as a signal for endocytic trafficking (29, 30) and infection The online version of this article contains supplemental material. with Kaposi’s sarcoma herpesvirus downregulates surface CD1d Abbreviations used in this paper: a-GalCer, a-galactosylceramide; AP, adaptor pro- through ubiquitination of the K326 residue, a presumed means of tein; b2m, b2-microglobulin; EE, early endosome; Endo H, endoglycosidase H; ER, immune evasion (31). endoplasmic reticulum; HC, H chain; hCD1d, human CD1d; LE, late endosome; MFI, In the current study, we have identified contrasting signals in the mean fluorescence intensity; MFIchl, MFI from chloroquine-treated cells; MFImon, MFI from monensin-treated cells; MFIveh, MFI from vehicle-treated cells; PNGase cytoplasmic tail of human CD1d important for its intracellular F, peptide:N-glycosidase F; SE, sorting endosome; TGN, trans-Golgi network; WT, distribution, endocytic trafficking, and ability to present Ag. Our wild-type. data strongly suggest that there are two major signals in the cy- Copyright Ó 2010 by The American Association of Immunologists, Inc. 0022-1767/10/$16.00 toplasmic tail that are important for lysosomal targeting. One www.jimmunol.org/cgi/doi/10.4049/jimmunol.0901448 4974 A THREONINE-BASED TARGETING SIGNAL FOR HUMAN CD1d directly targets the CD1d molecule to lysosomes and is Y331- CA). A PE-labeled goat anti-mouse Ig antiserum was purchased from based; the second is T322-based and, under normal conditions, DakoCytomation (Carpenteria, CA). A Texas Red-conjugated donkey anti- permits cell surface expression. When altered to mimic a phos- rabbit Ig antiserum was from Jackson ImmunoResearch Laboratories (West Grove, PA). A Texas Red-conjugated goat anti-mouse Ig antiserum phorylated form (T322D), CD1d is directed to lysosomes for and Hoechst stain were purchased from Molecular Probes (Portland, OR). degradation. The T322-based signal is dominant over that which is The HB95 hybridoma (pan-HLA class I-specific mAb) was a kind gift Y331-based and therefore controls the functional expression of from J. Yewdell and J. Bennink (Laboratory of Viral Diseases, National CD1d. We speculate that this type of threonine-based signal for Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD). Abs against the ER marker Sec61b were from Millipore targeting lysosomes also exists in many other type I transmembrane (Billerica, MA), whereas the anti-CD1d free H chain (HC)-specific mAb proteins and probably has a broad application in their intracellular (C3D5, for immunoprecipitation and Western analysis) was from Santa distribution and endocytic trafficking. Cruz Biotechnology (Santa Cruz, CA). A FITC-conjugated rabbit anti-PE Ab was obtained from Rockland Immunochemicals (Gilbertsville, PA). The CD1d-binding lipid a-GalCer was generated as described (35) or Materials and Methods purchased from Alexis Biochemicals (San Diego, CA). Recombinant hu- CD1d and mutant constructs man IL-2, IL-4, and GM-CSF were from PeproTech (Rocky Hill, NJ), whereas Ab pairs for the human IL-4 and GM-CSF ELISA assays (de- The wild-type (WT) human CD1d (hCD1d) cDNA was excised from scribed below) were obtained from BD Biosciences and Biolegend (San pBSKII-hCD1d (kindly provided by S. Balk, Harvard Medical School, Diego, CA), respectively. Peptide:N-glycosidase F (PNGase F) and en- Cambridge, MA) by XhoI/BamHI digestion (NEB, Ipswich, MA) and doglycosidase H (Endo H) were purchased from NEB. Monensin (BD inserted into the pcDNA3.1-neo vector (Invitrogen, Carlsbad, CA) to GolgiStop) was from BD Biosciences. generate pcDNA3.1-neo-hCD1d WT. The CD1d Y331A and TD-6 mutants were generated as described (13, 27) and also subcloned into pcDNA3.1- Culture of human NKT cells neo. The T322A and T322D mutants were generated by site-directed mutagenesis of pcDNA3.1-neo-hCD1d WT. The forward and reverse pri- Human NKT cells were generated following the protocol described by mers for T322A were 59-c att gtg ggc ttt gcc tcc cgg ttt aag-39 and 59-ctt Exley et al. (36). Briefly, human PBMCs were isolated from deidentified aaa ccg gga ggc aaa gcc cac aat g-39, respectively. The primers for T322D donated whole human blood (Indiana Blood Center, Indianapolis, IN) by were 59-c att gtg ggc ttt gac tcc cgg ttt aag-39 (forward) and 59-ctt aaa ccg density gradient centrifugation on Ficoll-Hypaque (GE Healthcare, Piscat- gga gtc aaa gcc cac aat g-39 (reverse). away, NJ). Va24-Ja18+ NKT cells were purified by positive selection using To generate hCD1d mutants in which the last 10 or all 14 cytoplasmic the 6B11 mAb followed by goat anti-mouse Ig coupled to magnetic beads tail amino acids were deleted (TD-10 and TD-14, respectively), two reverse (Miltenyi Biotec, Auburn, CA).
Load more

Recommended publications
  • Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse
    Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • Cd1b Tetramers Bind T Cell Receptors to Identify a Mycobacterial
    Published August 1, 2011 Brief Definitive Report CD1b tetramers bind T cell receptors to identify a mycobacterial glycolipid- reactive T cell repertoire in humans Anne G. Kasmar,1 Ildiko van Rhijn,1,2 Tan-Yun Cheng,1 Marie Turner,3 Chetan Seshadri,1 Andre Schiefner,4 Ravi C. Kalathur,4 John W. Annand,1 Annemieke de Jong,1 John Shires,5 Luis Leon,1 Michael Brenner,1 Ian A. Wilson,4 John D. Altman,5 and D. Branch Moody1 1Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115 2Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, Netherlands 3Tuberculosis Treatment Unit, Lemuel Shattuck Hospital, Jamaica Plain, MA 02130 4Department of Molecular Biology and Skaggs Institute for Chemical Biology, the Scripps Research Institute, La Jolla, CA 92037 Downloaded from 5Emory Vaccine Center, Atlanta, GA 30329 Microbial lipids activate T cells by binding directly to CD1 and T cell receptors (TCRs) or by indirect effects on antigen-presenting cells involving induction of lipid autoantigens, CD1 transcription, or cytokine release. To distinguish among direct and indirect mechanisms, we developed fluorescent human CD1b tetramers and measured T cell staining. CD1b tetramer staining of T cells requires glucose monomycolate (GMM) antigens, is specific for TCR jem.rupress.org structure, and is blocked by a recombinant clonotypic TCR comprised of TRAV17 and TRBV4-1, proving that CD1b–glycolipid complexes bind the TCR. GMM-loaded tetramers brightly stain a small subpopulation of blood-derived cells from humans infected with Mycobacterium tuberculosis, providing direct detection of a CD1b-reactive T cell reper- toire.
    [Show full text]
  • Flow Reagents Single Color Antibodies CD Chart
    CD CHART CD N° Alternative Name CD N° Alternative Name CD N° Alternative Name Beckman Coulter Clone Beckman Coulter Clone Beckman Coulter Clone T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells CD1a T6, R4, HTA1 Act p n n p n n S l CD99 MIC2 gene product, E2 p p p CD223 LAG-3 (Lymphocyte activation gene 3) Act n Act p n CD1b R1 Act p n n p n n S CD99R restricted CD99 p p CD224 GGT (γ-glutamyl transferase) p p p p p p CD1c R7, M241 Act S n n p n n S l CD100 SEMA4D (semaphorin 4D) p Low p p p n n CD225 Leu13, interferon induced transmembrane protein 1 (IFITM1). p p p p p CD1d R3 Act S n n Low n n S Intest CD101 V7, P126 Act n p n p n n p CD226 DNAM-1, PTA-1 Act n Act Act Act n p n CD1e R2 n n n n S CD102 ICAM-2 (intercellular adhesion molecule-2) p p n p Folli p CD227 MUC1, mucin 1, episialin, PUM, PEM, EMA, DF3, H23 Act p CD2 T11; Tp50; sheep red blood cell (SRBC) receptor; LFA-2 p S n p n n l CD103 HML-1 (human mucosal lymphocytes antigen 1), integrin aE chain S n n n n n n n l CD228 Melanotransferrin (MT), p97 p p CD3 T3, CD3 complex p n n n n n n n n n l CD104 integrin b4 chain; TSP-1180 n n n n n n n p p CD229 Ly9, T-lymphocyte surface antigen p p n p n
    [Show full text]
  • Targeting EZH2 Increases Therapeutic Efficacy of PD-1 Check-Point Blockade in Models of Prostate Cancer Supplement Figures and T
    Targeting EZH2 Increases Therapeutic Efficacy of PD-1 Check-Point Blockade in Models of Prostate Cancer Supplement Figures and Tables 1 Fig. S1. (A) Schema and genotyping PCR example for the creation of EM and EMC genetically engineered mice. (B) Three-dimensional PCa organoids generated from EM mice (without PSACreERT2) alleles. When treated with tamoxifen, demonstrates no loss of H3K27me3 or EDU staining, indicating specificity of tamoxifen-PSACreERT2 mediated deletion of the Ezh2 set domain. (C) Principle component analysis (PCA) following chemical and genetic inhibition of Ezh2 catalytic function results in significant changes in gene expression. 2 Fig. S2. (A) A 29-gene signature derived from Fig. 1C demonstrates complete independence from a previously published polycomb repression signature. (B) Our 29 gene signature demonstrates significant correlation with a previously published polycomb repression signature in 2 independent human PCa gene expression datasets. (C) EZH2 activity is not determined by EZH2 mRNA expression. 3 Fig. S3. A 29-gene signature derived from Fig 1C was used to generate signature scores for each patient within four independent human prostate cancer RNA-seq datasets. Patients were ranked highest score to lowest score and subject to quartile separation. First (blue) and fourth (red) quartiles were analyzed by supervised clustering to demonstrate expression differences within patients with most lowest EZH2 activity and most highest EZH2 activity. 4 Fig. S4. Genes representing IFN signaling (STAT1, IRF9), Th1 chemokines (CXCL10, CXCL11), and MHC Class I molecules (B2M, HLA-A) were shown to be enriched in PCa patients with low EZH2 activity. 5 Fig. S5. Treatment of 22Rv1 human 2D cell lines with the demonstrated conditions for 96 hours show that EZH2 inhibition increases expression of dsRNA (green = dsRNA, blue = nuclei).
    [Show full text]
  • Supplementary Table 1: Differentially Methylated Genes and Functions of the Genes Before/After Treatment with A) Doxorubicin and B) FUMI and in C) Responders Vs
    Supplementary Table 1: Differentially methylated genes and functions of the genes before/after treatment with a) doxorubicin and b) FUMI and in c) responders vs. non- responders for doxorubicin and d) FUMI Differentially methylated genes before/after treatment a. Doxo GENE FUNCTION CCL5, CCL8, CCL15, CCL21, CCR1, CD33, IL5, immunoregulatory and inflammatory processes IL8, IL24, IL26, TNFSF11 CCNA1, CCND2, CDKN2A cell cycle regulators ESR1, FGF2, FGF14, FGF18 growth factors WT1, RASSF5, RASSF6 tumor suppressor b. FUMI GENE FUNCTION CCL7, CCL15, CD28, CD33, CD40, CD69, TNFSF18 immunoregulatory and inflammatory processes CCND2, CDKN2A cell cycle regulators IGF2BP1, IGFBP3 growth factors HOXB4, HOXB6, HOXC8 regulation of cell transcription WT1, RASSF6 tumor suppressor Differentially methylated genes in responders vs. non-responders c. Doxo GENE FUNCTION CBR1, CCL4, CCL8, CCR1, CCR7, CD1A, CD1B, immunoregulatory and inflammatory processes CD1D, CD1E, CD33, CD40, IL5, IL8, IL20, IL22, TLR4 CCNA1, CCND2, CDKN2A cell cycle regulators ESR2, ERBB3, FGF11, FGF12, FGF14, FGF17 growth factors WNT4, WNT16, WNT10A implicated in oncogenesis TNFSF12, TNFSF15 apoptosis FOXL1, FOXL2, FOSL1,HOXA2, HOXA7, HOXA11, HOXA13, HOXB4, HOXB6, HOXB8, HOXB9, HOXC8, regulation of cell transcription HOXD8, HOXD9, HOXD11 GSTP1, MGMT DNA repair APC, WT1 tumor suppressor d. FUMI GENE FUNCTION CCL1, CCL3, CCL5,CCL14, CD1B, CD33, CD40, CD69, immunoregulatory and inflammatory IL20, IL32 processes CCNA1, CCND2, CDKN2A cell cycle regulators IGF2BP1, IGFBP3, IGFBP7, EGFR, ESR2,RARB2
    [Show full text]
  • Discovery of Deoxyceramides and Diacylglycerols As Cd1b Scaffold Lipids Among Diverse Groove-Blocking Lipids of the Human CD1 System
    Discovery of deoxyceramides and diacylglycerols as CD1b scaffold lipids among diverse groove-blocking lipids of the human CD1 system Shouxiong Huanga, Tan-Yun Chenga, David C. Younga, Emilie Layrea, Cressida A. Madigana, John Shiresb, Vincenzo Cerundoloc, John D. Altmanb, and D. Branch Moodya,1 aDepartment of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; bEmory Vaccine Center, Emory School of Medicine, Atlanta, GA 30322; and cMedical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom Edited* by Peter Cresswell, Yale University School of Medicine, New Haven, CT, and approved October 17, 2011 (received for review August 10, 2011) Unlike the dominant role of one class II invariant chain peptide (CLIP) environment (7, 8). The differing pH requirements for antigen in blocking MHC class II, comparative lipidomics analysis shows that loading, combined with enrichment of endogenous lipids in the human cluster of differentiation (CD) proteins CD1a, CD1b, CD1c, secretory pathway and exogenous lipids endosomes, are coalescing and CD1d bind lipids corresponding to hundreds of diverse accurate into a two-step model of lipid antigen presentation. First, newly mass retention time values. Although most ions were observed in translated CD1 proteins, aided by the microsomal triglyceride association with several CD1 proteins, ligands binding selectively to transport protein (MTP) (9),
    [Show full text]
  • Mechanisms and Consequences of Antigen Presentation By
    Series: The Biology of Antigen Presentation Feature Review Mechanisms and Consequences of Antigen Presentation by CD1 1, 1 1,2 Luc Van Kaer, * Lan Wu, and Sebastian Joyce The CD1 proteins are a family of non-polymorphic and MHC class I-related Trends molecules that present lipid antigens to subsets of T lymphocytes with innate- or The CD1–lipid presentation system adaptive-like immune functions. Recent studies have provided new insight into allows the immune system to sense alterations in lipid homeostasis, and the identity of immunogenic CD1 antigens and the mechanisms that control the complements the classical MHC–pep- generation and loading of these antigens onto CD1 molecules. Furthermore, tide presentation system. There are substantial progress has been made in identifying CD1-restricted T cells and remarkable similarities and surprising differences in the way that TCRs decoding the diverse immunological functions of distinct CD1-restricted T cell engage CD1–lipid versus MHC–pep- subsets. These findings shed new light on the contributions of the CD1 antigen- tide complexes. presentation pathway to normal health and to a diverse array of pathologies, and Group 1 CD1 proteins (CD1a–c) pre- provide a new impetus for exploiting this fascinating recognition system for the sent a variety of endogenous, myco- development of vaccines and immunotherapies. bacterial, and potentially other bacterial lipids to T cells. CD1b-restricted T cells include subsets expressing germline- Antigen-Presentation Systems encoded TCRs. Products encoded by the major histocompatibility complex (MHC) region of the vertebrate Group 2 CD1 proteins (CD1d) present genome bind peptide fragments from pathogens and display them at the surface of antigen- diverse endogenous and exogenous presenting cells (APCs) for appraisal by T lymphocytes [1].
    [Show full text]
  • Human CD Marker Chart Reviewed by HLDA1 Bdbiosciences.Com/Cdmarkers
    BD Biosciences Human CD Marker Chart Reviewed by HLDA1 bdbiosciences.com/cdmarkers 23-12399-01 CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD1a R4, T6, Leu6, HTA1 b-2-Microglobulin, CD74 + + + – + – – – CD93 C1QR1,C1qRP, MXRA4, C1qR(P), Dj737e23.1, GR11 – – – – – + + – – + – CD220 Insulin receptor (INSR), IR Insulin, IGF-2 + + + + + + + + + Insulin-like growth factor 1 receptor (IGF1R), IGF-1R, type I IGF receptor (IGF-IR), CD1b R1, T6m Leu6 b-2-Microglobulin + + + – + – – – CD94 KLRD1, Kp43 HLA class I, NKG2-A, p39 + – + – – – – – – CD221 Insulin-like growth factor 1 (IGF-I), IGF-II, Insulin JTK13 + + + + + + + + + CD1c M241, R7, T6, Leu6, BDCA1 b-2-Microglobulin + + + – + – – – CD178, FASLG, APO-1, FAS, TNFRSF6, CD95L, APT1LG1, APT1, FAS1, FASTM, CD95 CD178 (Fas ligand) + + + + + – – IGF-II, TGF-b latency-associated peptide (LAP), Proliferin, Prorenin, Plasminogen, ALPS1A, TNFSF6, FASL Cation-independent mannose-6-phosphate receptor (M6P-R, CIM6PR, CIMPR, CI- CD1d R3G1, R3 b-2-Microglobulin, MHC II CD222 Leukemia
    [Show full text]
  • Cd1b in Review: High TCR Specificity Limits Auto-Reactivity
    ISSN: 2574-1241 DOI: 10.26717/BJSTR.2019.12.002328 Radhashree Maitra. Biomed J Sci & Tech Res Review Article Open Access CD1b in Review: High TCR Specificity Limits Auto-Reactivity Nathaniel Elkaim and Radhashree Maitra* Department of Biology, Yeshiva University, New York, USA Received: : December 23, 2018; Published: : January 09, 2019 *Corresponding author: Radhashree Maitra, Department of Biology, Yeshiva University New York, USA Introduction Research of Alternative Presentation Pathways Antigen Presentation The immune system is commonly divided into two broad sections: innate immunity and adaptive immunity. Innate immunity While MHC efficiently presets protein antigens, other forms of the presentation of lipid antigens can be crucial in generating an antigens exist. With regards to microbial pathogens, specifically, effective immune response [1] (p. 314-5). Presentation of lipids is described as non-specific and hereditary whereas adaptive to T cells is accomplished via MHCI related proteins CD1 [19] and [1-5]. The adaptive immune system has two functional cell types: immunity is characterized by high specificity encoded somatically MR1 [20], which contain an α chain and non-covalently associated T cells and B cells [6-10]. While B cells participate in humoral β -microglobulin. The understanding of alternate presentation immunity by releasing antibodies into the body to opsonize or 2 incapacitate foreign bodies, cytotoxic T cells attack individual cells restricted T cells was published in 1989, but the nature of the antigen that may be compromised. This system of developing immunity systems has developed slowly. The first paper describing CD1- T cells [11]. presented was not precisely identified. The emergence of lipids as T against a specific antigen is dependent on antigen presentation to years later by the discovery of the antigenic properties of mycolic cell antigens presented by CD1 molecules was only established five The MHC Pathway acid.
    [Show full text]
  • Cells and Marginal Zone B Cells CD1.1 Expression by Mouse Antigen-Presenting
    CD1.1 Expression by Mouse Antigen-Presenting Cells and Marginal Zone B Cells Jessica H. Roark, Se-Ho Park, Jayanthi Jayawardena, Uma Kavita, Michele Shannon and Albert Bendelac This information is current as of September 29, 2021. J Immunol 1998; 160:3121-3127; ; http://www.jimmunol.org/content/160/7/3121 References This article cites 48 articles, 26 of which you can access for free at: Downloaded from http://www.jimmunol.org/content/160/7/3121.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: by guest on September 29, 2021 http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. CD1.1 Expression by Mouse Antigen-Presenting Cells and Marginal Zone B Cells1 Jessica H. Roark, Se-Ho Park, Jayanthi Jayawardena, Uma Kavita, Michele Shannon, and Albert Bendelac2 Mouse CD1.1 is an MHC class I-like, non-MHC-encoded, surface glycoprotein that can be recognized by T cells, in particular NK1.11 T cells, a subset of ab T cells with semiinvariant TCRs that promptly releases potent cytokines such as IL-4 and IFN-g upon stimulation.
    [Show full text]
  • Intracellular Pathways of Cd1 Antigen Presentation
    REVIEWS INTRACELLULAR PATHWAYS OF CD1 ANTIGEN PRESENTATION D. Branch Moody* and Steven A. Porcelli‡ 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. For many years, it was thought that peptides were the phosphatidylinositols, sphingolipids and polyiso- only structurally varied targets of T-cell responses. The prenoid lipids10–15. These known antigens, together discovery of CD1-dependent antigen-presentation with diffferentially glycosylated derivatives of these pathways provided a mechanism by which T cells can lipids that might function as antigens, form a poten- specifically recognize an array of lipids and glycolipids tially large pool of structures that could be recognized that comprise the membranes of mammalian cells and by CD1-restricted T cells. Although certain CD1D- microbial pathogens1. Mouse CD1d, and guinea-pig restricted natural killer T (NKT) cells use TCRs of lim- CD1b and CD1c, as well as four of the five human ited diversity, the available evidence indicates that the CD1 proteins (CD1A, CD1B, CD1C and CD1D), have CD1-restricted T-cell repertoire also includes T cells been shown to bind and present lipid antigens to with substantial TCR diversity16–20.
    [Show full text]