Stains & CD markers
CD1-9


Topic Completed: 1 July 2013

Minor changes: 29 June 2021

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PubMed Search: CD1 [TI] "last 5 years"[dp], CD2[TI] review[ptyp], CD6, CD7[title], CD9[title]

Nat Pernick, M.D.
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Cite this page: Pernick N. CD1-9. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd1.html. Accessed October 16th, 2021.
CD1
  • Family of nonpolymorphic MHC class I-like glycoproteins on surface of various antigen presenting cells; member of immunoglobulin superfamily
  • Mediate presentation of endogenous and foreign lipids (including bacterial lipid antigens) on cell surface for recognition by T cell receptors
  • To sample a diverse antigen pool, CD1 proteins are repeatedly internalized and recycled; this may be assisted by lipid transfer proteins such as saposins (J Biol Chem 2013;288:19528, Proc Natl Acad Sci USA 2012;109:4357)
  • May also mediate thymic T cell development
  • Has 5 different subsets (CD1a, CD1b, CD1c, CD1d, CD1e), all noncovalently associated with beta 2 microglobulin, all on #1q22-23 (non MHC linked)
  • Different CD1 forms bind to different types of lipid antigen based on differences in their antigen binding grooves (Nat Rev Immunol 2005;5:387)
  • Separated into 2 groups based on sequence homology:
  • Pathophysiology:
    • Cellular infection with Mycobacteria tuberculosis or exposure to mycobacterial cell wall products converts CD1- myeloid precursors into competent CD1+ antigen presenting cells (J Immunol 2005;175:1758)
      • However M. tuberculosis possesses a successful tactic based, at least in part, on CD1 downregulation to evade CD1 dependent immunity (Clin Dev Immunol 2011;2011:790460)
    • Pollen lipids are also recognized as antigens by T cells via CD1 dependent pathway (J Exp Med 2005;202:295)
  • Clinical features:
  • Uses by pathologists: CD1a is used to diagnose Langerhans cell histiocytosis and to exclude other entities that are CD1a negative
CD1a
CD1b
  • On chromosome 1q22-23 (not MHC linked); noncovalently associated with beta2 microglobulin
  • Capable of binding ligands with greatly varying alkyl chain lengths (including Mycobacteria tuberculosis and Mycobacteria leprae) through a complex network of interconnected hydrophobic pockets (J Immunol 2004;172:2382, Proc Natl Acad Sci USA 2011;108:19335, OMIM: 188360 [Accessed 13 May 2021])
  • Part of immune response to intracellular bacteria
  • Human gammadelta T cells recognize Lipid A in a CD1b or CD1c restricted manner as a first response to gram negative bacteria (Biol Direct 2009;4:47)
  • No significant clinical use by pathologists
  • Positive staining - normal: cortical thymocytes, Langerhans cells (weaker staining than CD1a), myeloid dendritic cells, brain pyramidal cells and subpopulation of B cells
  • Positive staining - disease:
  • Negative staining: normal B cells
CD1c
  • On chromosome 1q22-23 (not MHC linked); noncovalently associated with beta2 microglobulin
  • Mediates the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells (Immunity 2010;33:853)
  • Has the capacity to present a wide repertoire of antigens to reactive T cells (Mol Immunol 2013;55:182, J Biol Chem 2011;286:37692)
  • Expressed on a subset of myeloid dendritic cells; secrete IL10 in response to Escherichia coli (Eur J Immunol 2012;42:1512)
  • Common CD1c antibody is BDCA1
  • Clinical features:
  • No significant clinical use by pathologists
  • Positive staining - normal:
    • Cortical thymocytes, Langerhans cells (weaker staining than CD1a), immature myeloid dendritic cells (J Clin Invest 2007;117:2517)
    • Subset of normal peripheral B cells, subset of activated T cells
  • Positive staining - disease:
  • Negative staining: normal B cells
  • Electron microscopy description: present in early and late endosomes (J Exp Med 2000;192:281)
CD1d
  • CD1d presents lipid antigens to natural killer T (NKT) cells; when activated, NKT cells rapidly produce Th1 and Th2 cytokines, typically represented by interferon gamma and IL4 (Wikipedia: CD1D [Accessed 31 July 2018], OMIM: 188410 [Accessed 31 July 2018])
  • B cells also present lipid antigen to CD1d restricted invariant NKT cells, which contributes to maintaining tolerance in autoimmunity
  • On chromosome 1q22-23 (not MHC linked)
  • Also called R3G1
  • Sole group 2 member of the CD1 family of MHC-like glycoproteins
  • Clinical features:
  • Uses by pathologists: no significant clinical use by pathologists; may play a role in future vaccine development (Proc Natl Acad Sci U S A 2010;107:13010)
  • Case reports: 6 year old boy with no apparent immunodeficiency who suffered severe life threatening infection with varicella vaccine virus, with low invariant natural killer T cells and diminished CD1d expression (J Infect Dis 2011;204:1893)
  • Positive staining - normal:
  • Positive staining - disease: some B and T cell malignancies; keratinocytes in psoriasis
  • Negative staining: normal B cells
CD1e
  • Participates in lipid antigen presentation without interacting with T cell receptor; binds lipids in lysosomes and facilitates processing of complex glycolipids, thus promoting editing of lipid antigens; may positively or negatively affect lipid presentation by CD1b, CD1c, CD1d (Proc Natl Acad Sci USA 2011;108:14228)
  • Only CD1 protein existing in soluble form in late endosomes of dendritic cells; not expressed on cell surface
  • On chromosome 1q22-23 (not MHC linked); noncovalently associated with beta2 microglobulin
  • Clinical features:
    • Processes mycobacterial antigen (instead of presenting antigen directly) and may help expand repertoire of glycolipid T cell antigens to optimize the immune response (Science 2005;310:1321, Proc Natl Acad Sci USA 2011;108:13230)
    • Initially accumulates in Golgi of immature dendritic cells or transfected cells as a membrane associated form, then is transported to early and then late endosomes, then is cleaved into a soluble form, which facilitates the processing of glycolipids presented by other CD1 molecules transiting through the same compartments (Biochem J 2009;419:661)
    • +6129 A/G gene polymorphisms are associated with multiple sclerosis (Immunol Invest 2010;39:874)
  • No significant clinical use by pathologists
  • Positive staining - normal: dendritic cells
CD2
  • Early T cell marker expressed on all peripheral blood T cells, 95% of thymocytes, NK cells but no B cells (OMIM: 186990 [Accessed 13 May 2021], J Biol Chem 2010;285:41755)
  • Gene is at 1p13.1; protein is member of immunoglobulin superfamily
  • Also called E rosette receptor because CD2 antibodies inhibit formation of rosettes with sheep erythrocytes
  • Also called LFA2 (leukocyte function antigen), T11
  • Pathophysiology:
    • Binds CD58 (LFA3) on antigen presenting cells, which enables T cells to respond to lower concentrations of antigen (J Exp Med 1999;190:1383)
    • Mediates adhesion between T cells and antigen presenting cells, induces costimulatory signals in T cells and T cell cytokine production, inhibits apoptosis of activated peripheral T cells (Immunology 2013;139:48)
    • Regulates T cell anergy
    • Regulates T and NK mediated cytolysis
    • CD2 distinguishes 2 subsets of human plasmacytoid dendritic cells with distinct phenotype and functions (J Immunol 2009;182:6815)
    • CD2 promotes NK cell membrane nanotube formation (PLoS One 2012;7:e47664)
  • Clinical features:
  • Uses by pathologists: T cell marker (membranous staining), although CD3 is more commonly used; marker of systemic mastocytosis
  • Positive staining - normal:
    • Thymocytes (95%), mature peripheral T cells (almost all), NK cells (80 - 90%), mast cells
    • Variable thymic B cells (50%), Langerhans cells
  • Positive staining - disease:
CD2R
  • CD2 epitope present on activated T cells, unmasked by conformational change of CD2 glycoprotein during activation
  • No recent articles in literature
  • No significant clinical use by pathologists
  • Positive staining - normal: activated T cells
  • Positive staining - disease: blood and synovial fluid T cells in rheumatoid arthritis; peripheral blood T cells in juvenile rheumatoid arthritis, SLE, ankylosing spondylitis and Lyme disease (Scand J Immunol 1991;34:351)
  • Negative staining: resting T cells
CD3
CD4
CD5
CD6
CD7
CD8
CD9
  • Cell surface protein that mediates adhesion, migration, signal transduction
  • Also called tetraspanin CD9, motility related protein 1 (MRP1) (note: MRP is multidrug resistance associated protein)
  • Antibodies are used to purge bone marrow in acute lymphoblastic leukemia prior to peripheral stem cell bone marrow transplant (Am J Pediatr Hematol Oncol 1993;15:162)
  • Pathophysiology:
    • Member of transmembrane 4 superfamily (tetraspanin family); tetraspanins have 4 hydrophobic domains, organize multimolecular complexes in plasma membrane; each tetraspanin associates specifically with integrins and other tetraspanins, forming primary complexes and leading to molecular network of interactions, the "tetraspanin web"
    • Regulates cell motility, development, activation, growth and adhesion (Blood 2011;117:1840)
    • Regulates paranodal junction formation (between neurons and glia)
    • Required for microparticle release from coated platelets (Platelets 2009;20:361)
      • Triggers platelet activation and aggregation
    • Supports myotube maintenance and promotes muscle cell fusion
    • Downregulation in ovarian carcinoma may promote tumor dissemination (Cancer Res 2005;65:2617)
    • May suppress metastasis in small cell lung cancer by promoting apoptosis via calretinin expression (Cancer Res 2010;70:8025, FEBS Open Bio 2013;3:225)
    • May mediate invasion by upregulating MMP9 (PLoS One 2013;8:e67766)
  • Clinical features:
  • No significant clinical use by pathologists
  • Positive staining - normal:
    • Pre B cells, B cell subset, activated T cells, basophils, eosinophils (Am J Respir Cell Mol Biol 2012;46:188)
    • Macrophages, megakaryocytes, plasma cells, plasma cell precursors in germinal centers (Biochem Biophys Res Commun 2013;431:41), platelets
    • Brain, cardiac muscle, GI system, kidney (glomeruli, tubules and collective ducts), liver, lymphatic epithelium, ovarian surface epithelium, peripheral nerve, skin, spleen, thyroid, tonsil
  • Positive staining - disease:
  • Negative staining: red blood cells, renal collecting duct carcinomas (almost all)
Diagrams / tables

Images hosted on other servers:
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CD1d: antigen presentation

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CD1d: viral evasion of antigen presentation

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CD1d: intestinal epithelial CD1d expression

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CD2: T cells and antigen presenting cells

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CD9: structure

Microscopic (histologic) images

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CD1: primary and metastatic melanoma

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CD1: Langerhans cells of anal mucosa

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CD1b: leprosy patient

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CD1c: marginal zone B cells (spleen)

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CD1c: stomach: H. pylori+ mucosa

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CD1c: thyroid gland


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CD1c: immature dendritic cells

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CD1d: HPV associated lesions (cervix)

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CD1d: paracortical dendritic cells (lymph nodes)

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CD1d: trophoblast (placenta)

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CD1d: scalp skin


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CD2: hepatosplenic T cell lymphoma (liver biopsy)

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CD2: hydroa
vacciniforme-like
lymphoma

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CD2: anaplastic large cell lymphoma (lymph node)

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Brain (CD6-)

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CD6: colon


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Kidney (CD6-)

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Skeletal muscle (CD6-)

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CD6: tonsil

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Uterus (CD6-)

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CD7: normal tonsil

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CD7: cutaneous T cell lymphoma


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CD7+ anaplastic large cell lymphoma

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CD7+
angioimmunoblastic
T cell lymphoma

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CD9: normal tissue (cerebrum)


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CD9: normal tissue (cervical squamous epithelium)

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CD9: cervical carcinoma

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CD9: CNS nonneuroepithelial tumors


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CD9: well differentiated adenocarcinoma (gallbladder)

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CD9: mesothelioma

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CD9: basal and
squamous cell
carcinoma and
actinic keratosis

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CD9: small cell lung cancer

Electron microscopy images

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CD1c: various cellular locations

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