DNA实验-免疫细胞表面抗原分子CD家族对照表CD1-CD24

免疫细胞表面抗原分子CD家族对照表(CD1-CD247)

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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: AJSP 2001;25:630

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: AJSP 2001;25:1413

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 < % 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: Mod Path 2002;15:1131

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 , 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