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Note: no information is available on CDw145, CD181, CD182, CD185-194, CD196-199, CD211, CD214-216, CD218-220, CD237
Background
CD: cluster designation of monoclonal antibodies (clusters of differentiation)
Designated at the 1st to 7th Workshops on International Human Leukocyte Differentiation Antigens
The last conference was in 2000. The next conference is in 2004.
HLDA Workshops are the primary mechanism to characterize leukocyte surface antigenic molecules and epies; erythroid antigens are now included
For 1st to 6th workshops, antibodies were submitted to the organizing laboratory, coded and sent to participating laboratories for testing against various cell types. For the 7th workshop, a CD designation could be established for a molecule if its gene has been cloned and at least one specific monoclonal antibody had been studied in the Workshop
Interpretation should be based on cellular distribution of staining, proportion of positively stained cells, staining intensity and cutoff levels.
CD1
Family of non-polymorphic MHC class I-like glycoproteins
Also member of immunoglobulin superfamily
On chromosome 1q22-23 (not MHC linked)
Has 5 different subsets, all noncovalently associated with 12 kd beta 2 microglobulin
Function: restrict T cell responses to certain antigens; may mediate thymic T cell development
Positive staining (normal): cortical thymocytes (70%), activated T cells, Langerhans cells, interdigitating dendritic cells
Positive staining (disease): pre T ALL with cortical thymocyte phenotype; Langerhans cell histiocytosis
Negative staining: mature peripheral T cells
CD1a
Positive staining (normal): Dendritic cells in dermis/epidermis of benign inflammatory skin disorders
Positive staining (disease): Langerhans cell histiocytosis (fairly specific), myeloid leukemias, some B cell malignancies; dendritic cells in most peripheral cutaneous T cell lymphomas, AJCP 2001;116:72
Negative staining: normal B cells, most cutaneous peripheral B cell lymphomas (? reflects replacement of reactive pattern containing dendritic cells with a neoplastic pattern of B cells)
Micro images: Langerhans cell histiocytosis
Micro images (AJSP subscribers): pulmonary Langerhans cell histiocytosis
Micro images (Hum Path subscribers): Langerhans cell histiocytosis
References:
CD1b
Positive staining (disease): myeloid leukemias and some B cell malignancies
Negative staining: normal B cells
CD1c
Positive staining (normal): subset of normal peripheral B cells
Positive staining (disease): myeloid leukemias and some B cell malignancies
Negative staining: normal B cells
CD1d
Positive staining (normal): thymus (low levels), bowel
CD1e
CD2
Aka E rosette receptor, LFA-2 (leukocyte function antigen)
Function: binds CD58 / LFA-3 on antigen-presenting cells, and induces costimulatory signals in T cells
Also regulates T and NK-mediated cytolysis, inhibits apoptosis of activated peripheral T cells, mediates T cell cytokine production, regulates T cell anergy
Positive staining (normal): thymocytes (95%), mature peripheral T cells (almost all), NK cells (80-90%), thymic B cells (50%)
Micro images: extranodal NK/T cell lymphoma, nasal type
CD2R
CD2 epies restricted to activated T cells
Positive staining: activated T cells, ? NK cells
CD3
Aka OKT3
Function: complex (5 chains) of integral membrane glycoproteins assembled as a complex; has long cylasmic tail with antigen recognition activation motif; complex is then down regulated
Also subdivided into delta, epsilon, gamma subtypes
Cylasmic expression at early T cell differentiation, then membranous expression
Most specific T cell antibody
Positive staining (normal): thymocytes, peripheral T cells, NK cells; also Purkinje cells of cerebellum
Positive staining (disease): 80% of T cell lymphomas
Negative staining: gamma delta T cell receptors, most B cell lymphomas
Micro images: CD3 epsilon-testicular NK/T cell lymphoma (figure 3D)
Micro images (AJSP subscribers): achalasia, post-transplant lymphoproliferative disease in liver
References:
CD4
Aka OKT4, T helper/inducer
On chromosome #12p
Nonpolymorphous glycoproteins belonging to immunoglobulin superfamily
Serves as HIV receptor on T cells (as do chemokine receptors CCR5 and CXCR4), macrophages, brain
CD4+ T cells are killed by HIV
Coreceptor in MHC class II-restricted antigen induced T cell activation
Binds to nonpolymorphic region of class I molecules; may increase avidity of cell-cell interactions
Positive staining (normal): thymocytes (80-90%), mature T cells (65%, T helper and CD4/CD8+ thymocytes), macrophages, Langerhans cells, dendritic cells, granulocytes
Positive staining (disease): pityriasis lichenoides
Micro images: acute demyelinating disease, extranodal NK/T cell lymphoma, nasal type
CD5
Belongs to ancient scavenger receptor family
Is physically and functionally coupled with T cell receptor-zeta-CD3 signal transducer complex
CD5+ B cells produce “generalist antibodies” - polyreactive low affinity "natural" antibodies to exogenous antigens (tetanus toxoid, lipopolysaccharide) as well as autoreactive antibodies (ssDNA, thyroglobulin, insulin)
Note: sharks only have polyreactive IgM
Note: monoreactive IgG is produced by < 0.1% of circulating B cells, from positive selection and somatic
point mutation
First line of defense against antigens; have a low activation threshold; are the only line of defense for those who cannot produce specific antibody
Produce antibodies using germ line (non mutated) configuration of gene segments, usually IgM
Production elevated in rheumatoid arthritis (27-52% of circulating B cells vs. 20% normal)
CD5 may serve as a dual receptor, giving either stimulatory or inhibitory signals depending both on the cell type and the development stage
Positive staining (normal): B cells of mantle zone of spleen and lymph nodes; B cells in peritoneal and pleural cavities; almost all T cells;
In fetus, most B cells in spleen and cord blood are CD5 positive
Positive staining (disease): B cell CLL/SLL, mantle cell lymphoma, most T malignancies, thymic carcinomas (70%)
Negative staining: spindle cell thymomas, MALT lymphoma, follicular lymphoma
Micro images: extranodal NK/T cell lymphoma, nasal type, mantle cell lymphoma (figure 3D)
CD6
Adhesion molecule mediating the binding of developing thymocytes with thymic epithelial cells
May be involved in autoimmunity and graft vs. host disease (GVHD)
Antibodies to CD6 are used to deplete T cells from bone marrow transplants to prevent GVHD
Positive staining (normal): low levels on immature thymocytes, high levels on mature thymocytes
CD7
Membrane glycoprotein and Fc receptor for IgM
Homologous to TCR gamma, Ig kappa
Membrane expression early during T ontogeny, before TCR rearrangement, persists until terminal stages of T cell development
Lower expression in memory T cells vs. naive T cells
Positive staining (normal): mature peripheral T cells (85%), post-thymic T cells (majority), NK cells (majority), some myeloid cells
Positive staining (disease): T cell ALL; AML (especially M4/M5), chronic myelogenous leukemia, blasts in transient myeloproliferative disorder
Negative expression: B cell ALL, Sezary syndrome, adult T cell leukemia/lymphoma
Micro images: extranodal NK/T cell lymphoma, nasal type
CD8
Aka OKT8, T cell suppressor/cytotoxic cells
On chromosome #2
MHC class I restricted receptor; binds to nonpolymorphic region of class I molecules; may increase avidity of cell-cell interactions
Associated with lymphoepithelioma-like carcinoma of lung (AJSP 2002;26:715)
Positive staining (normal): T cells (25-35% of mature peripheral T cells, most cytotoxic T cells, CD4/CD8+ thymocytes); NK cells (30%-which are also CD3 negative); cortical thymocytes (70-80%), epidermotrophic lymphocytes in mycosis fungoides (AJSP 2002;26:450)
Micro images: lymphoepithelioma-like carcinoma of cervix-figure 3, acute demyelinating disease
Micro images (Mod Path subscribers): nodal cytotoxic T cell lymphoma
Reference:
CD9
May mediate platelet activation and aggregation
Antibodies are used to purge bone marrow prior to peripheral stem cell bone marrow transplant
Viral co-receptor
Positive staining (normal): pre B cells, B cell subset, T cells, macrophages, platelets, eosinophils, basophils, megakaryocytes, endothelial cells, brain, peripheral nerve, vascular smooth muscle, cardiac muscle, epithelia
CD10
Aka Common Acute Lymphoblastic Leukemia Antigen (CALLA), neutral endopeptidase 24.11, neprilysin, enkephalinase
Cell membrane metallopeptidase, characteristic marker of follicular center cells and follicular lymphoma, but also widely distributed in normal tissue and neoplasms; also localized to brush border in small bowel mucosa
Inactivates bioactive peptides
Uses:
Acute lymphoblastic leukemia: one of first markers to identify leukemic cells in children (hence its name)
Breast: marker of myoepithelial cells, Mod Path 2002;15:397
Burkitt lymphoma: confirm diagnosis
Colonic carcinogenesis: increase in stromal cells from mild to severe dysplasia to invasive carcinoma, Hum Path 2002;33:806-811
Endometriosis: helpful in identifying areas of endometriosis if sparse glandular tissue
Follicular lymphoma: to confirm diagnosis
Hepatocellular carcinoma vs. nonhepatocellular carcinomas: 68% sensitive and >95% specific with canalicular pattern, AJSP 2001;25:1297, AJSP 2002;26:978, although another study recommends Hepatocyte, MOC31, and pCEA but not CD10, Mod Path 2002;15:1279
Microvillous inclusion disease: strong CD10+ cylasmic staining vs. linear brush border staining in normals, AJSP 2002;26:902
Positive staining (normal): adrenal cortex, pre-B cells, brain, choroid plexus, cortical thymocytes, endometrial stroma, follicular center cells, granulocytes, kidney microvilli, liver, lymphohemaoietic precursors, male GU epithelium, mesonephric remnants, myoepithelial cells (breast), neutrophils, ovary, placenta (cytotrophoblast, intermediate trophoblast, syncytiotrophoblast), small intestine (linear brush border staining)
Positive staining (disease): adenomyosis of endometrium, preB ALL (75%), CML in blast crisis (90%), colonic carcinoma, dermatofibroma, dermatofibrosarcoma, endometrial adenocarcinoma (may be present in desmoplastic stroma), endometrial stromal tumors, follicular center cell lymphomas, gastric carcinoma, glioma, hepatocellular carcinoma (canalicular pattern similar to polyclonal CEA), malignant mixed mullerian tumors, mediastinal germ cell tumors, melanomas, mesonephric tumors, microvillous inclusion disease (strong cylasmic staining), mullerian adenosarcoma, pancreatic adenocarcinoma, pancreatic solid-pseudopapillary tumor, placental site trophoblastic tumor, primary mediastinal B cell lymphomas (some), prostate carcinoma, renal cell carcinoma, renal cell sarcoma, rhabdomyosarcoma and other sarcomas, schwannoma, tumor of wolffian origin of broad ligament and ovary, urothelial carcinoma, uterine carcinoma, uterine cellular leiomyomas (50%), uterine leiomyosarcomas and other uterine sarcomas
Negative staining: myeloid and erythroid precursors, other female genital tract tumors (including clear cell carcinomas)
Micro images: follicular center cells (figure 1), intranodal heteroic mammary ducts (figure 1C),
Micro images (AJSP subscribers): endometrial stromal tumor #1 (negative), #2, hepatocellular carcinoma#1, #2, mesonephric carcinoma of uterus, mesonephric derivatives in men, microvillous inclusion disease#1, #2 (controls), vulvar, vaginal and cervical lesions, uterus and trophoblast, fallopian tube and ovary
Micro images (Hum Path subscribers): canalicular pattern in hepatocellular carcinoma (figure C), gastric carcinoma at apical border (figure B), colonic adenoma, colonic carcinoma#1, #2
Micro images (Mod Path subscribers): canalicular pattern in hepatocellular carcinoma (figure B), malignant mixed mullerian tumor#1, #2, #3, breast myoepithelium, breast adenosis, breast DCIS, invasive ductal carcinoma of breast, diffuse large B cell lymphoma, adenomyosis
References: AJSP 2002;26:978, AJSP 2001;25:1540, AJSP 2002;26:902, AJSP 2003;27:178, Mod Path 2002;15:1279, Mod Path 2002;15:923, Mod Path 2002;15:397, Mod Path 2002;15:413, Mod Path 2002;16:22
CD11
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