Carcinoembryonic antigens (CD66) on epithelial cells and neutrophils are receptors for Opa proteins of pathogenic neisseriae.
Opa protein-expressing pathogenic neisseriae interact with CD66a-transfected COS (African green monkey kidney) and CHO (Chinese hamster ovary) cells. CD66a (BGP) is a member of carcinoembryonic antigen (CEA, CD66) family. The interactions occur at the N-terminal domain of CD66a, a region that is highly conserved between members of the CEA subgroup of the CD66 family. In this study, we have investigated the roles of CD66 expressed on human epithelial cells and polymorphonuclear phagocytes (PMNs) in adhesion mediated via Opa proteins. Using human colonic (HT29) and lung (A549) epithelial cell lines known to express CD66 molecules, we show that these receptors are used by meningococci. A monoclonal antibody, YTH71.3, against the N-terminal domain of CD66, but not 3B10 directed against domains, A1/ B1, inhibited meningococcal adhesion to host cells. When acapsulate bacteria expressing Opa proteins were used, large numbers of bacteria adhered to HT29 and A549 cells. In addition, both CD66a-transfected CHO cells and human epithelial cells were invaded by Opa-expressing meningococci, suggesting that epithelial cell invasion may occur via Opa-CD66 interactions. In previous studies we have shown that serogroup A strain C751 expresses three Opa proteins, all of which mediate non-opsonic interactions with neutrophils. We have examined the mechanisms of these interactions using antibodies and soluble chimeric receptors. The results indicate that the nature of their interactions with purified CD66a molecules and with CD66 on neutrophils is alike and that these interactions occur at the N-terminal domain of CD66. Thus, the Opa family of neisserial ligands may interact with several members of the CD66 family via their largely conserved N-terminal domains.
Virji
M
M
Department of Paediatrics, University of Oxford, John Radcliffe Hospital, UK. mumtaz.virji@paediatrics.oxford.ac.uk
Makepeace
K
K
Ferguson
D J
DJ
Watt
S M
SM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D016466:CHO Cells; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000276:immunology*; D006224:Cricetinae; D019073:HT29 Cells; D006801:Humans; D008854:Microscopy, Electron; D009345:Neisseria meningitidis / Q000276:immunology*; D010587:Phagocytosis; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C050308:opacity proteins