CD66 identifies a neutrophil-specific epitope within the hematopoietic system that is expressed by members of the carcinoembryonic antigen family of adhesion molecules

Abstract

Preliminary results from the IVth Leucocyte Culture Conference have classified the monoclonal antibody (MoAb), YTH 71.3.2, as CD66. Two other MoAbs, YPC 2/12.1 and CE6/2D3.1, share a common cellular specificity, reacting with cells of the neutrophil series and colonic epithelium. The YTH 71.3.2 and CE6/2D3.1 MoAbs both recognize a similar CD66 defined epitope that is distinct from that identified by YPC 2/12.1. By Western blotting, these antibodies react with different molecular species from cells of different lineages. The antibodies identify 50- to 55-Kd, 80- to 100-Kd, and 130- to 200-Kd components present in a semi-purified carcinoembryonic antigen (CEA) preparation from colonic adenocarcinomas and a 90- to 130-Kd molecule from HL-60 cells. With the colonic cell line, LS174T, YPC2/12.1 stains diffuse bands of 160 to 200 Kd and 90 to 130 Kd with equal intensity, whereas the binding of CE6/2D3.1 and YTH 71.3.2 is biased toward the lower molecular weight set of molecules. Remarkably, all three antibodies recognize CEA-related molecules. Defined analyses using HeLa cells transfected with CEA, NCA(NCA-50/90), and CGM6(NCA-95) cDNAs show that the three MoAbs identify CEA to varying degrees. While YTH 71.3.2 and CE6/2D3.1 also bind to NCA-50/90, YPC 2/12.1 recognizes an epitope expressed by both the NCA-50/90 and NCA-95 molecular species.

Nonopsonic Phagocytosis of Group C Neisseria meningitidis by Human Neutrophils

“…Recently, a different neutrophil receptor for meningococcal Opa proteins was suggested, i.e., the CD66a adhesion molecule (biliary glycoprotein), which belongs to the carcinoembryonic antigen family (50,51). The CD66 cluster of antigens includes structurally related glycoproteins that are members of the larger immunoglobulin supergene family and are upregulated by neutrophil activation (43,52,53). They have also been found to activate neutrophils and play a role in neutrophil effector function (20,42,45,46).…”

An alternative flow cytometry strategy for peripheral blood dendritic cell enumeration in the setting of repetitive GM-CSF dosing

“…In pursuing our objective of developing an alternative strategy to provide enumeration of the broader circulating myeloid DC pool than reported lineage cocktails that would be applicable to whole blood flow cytometry analysis and retain the ability to evaluate functional capacity, we investigated several potential substitute cell surface antigens that are not expressed on monocytes. CD66 proved to be the most attractive candidate marker due to its expression on granulocytes, NK cells, lymphocytes, and macrophages and absence of reported expression on DCs [ 48 - 55 ]. The report of reactivity in macrophages and macrophage-like myelomonocytic cell lines raised concerns for as yet unrecognized expression on myeloid DCs.…”

“…We postulated that an antibody cocktail that would identify granulocytes, NK cells, lymphocyte lineages, and activated monocytes in whole blood analyses would potentially provide a more accurate enumeration of circulating DCs. Members of the CD66 family, recognized by commercially available monoclonal antibodies, are widely expressed on granulocytes, NK cells, lymphocytes, and activated monocytes/macrophages [ 48 - 55 ] and provide candidate antibodies for a lineage negative cocktail that would permit more consistent identification of the circulating DC population, even in the setting of repeated administration of the biological adjuvant, GM-CSF.…”

Synthetic peptides from the N‐domains of CEACAMs activate neutrophils

“…The structure of the N‐domain is predicted to be a stacked pair of β‐sheets with nine β‐strands (7). CD66 mAbs react with members of the CEACAM family (8–17). In CD terminology, mAbs belonging to the CD66 cluster are classified according to their reactivity with each family member, as indicated by a lower case letter after ‘CD66’ as follows: CD66a, CEACAM1 or biliary glycoprotein; CD66b, CEACAM8; CD66c, CEACAM6; CD66d, CEACAM3; CD66e, CEA; and CD66f, pregnancy‐specific glycoprotein (PSG) (6,13).…”

“…CEACAMs may function as adhesion molecules and can also transmit signals. CEACAM1, CEACAM6 and CEA are capable of homotypic and heterotypic adhesion, whereas CEACAM8 undergoes heterotypic adhesion with CEACAM6, as shown by use of recombinant CEACAM proteins (3,4,8–12,14–34). CEACAM1, CEACAM8, CEACAM6 and CEACAM3, but not CEA, are expressed on human neutrophils, where they are ‘activation antigens’ in that their surface expression is increased following neutrophil activation by various stimuli.…”