Carcinoembryonic antigens (CD66) on epithelial cells and neutrophils are receptors for Opa proteins of pathogenic neisseriae

Abstract

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.

Selection for a CEACAM Receptor-Specific Binding Phenotype during Neisseria gonorrhoeae Infection of the Human Genital Tract

“…Finally, it is pertinent to note that, while none of the recombinant Opa variants tested to date are able to bind to CEACAM8 (16,18,19), several isolates showed very low-level binding to CEACAM8-expressing cells (Fig. 3), whereas none bound to the untransfected Lec11 cell line (data not shown).…”

“…N. gonorrhoeae isolates from both naturally infected men and women are predominantly Opa ϩ , as are isolates obtained from men experimentally infected with transparent (Opa phase-varied off) colonies (12)(13)(14). Most gonococcal Opa variants bind to one or more members of the human CEACAM family of receptors (15)(16)(17)(18)(19)(20). CEACAM receptors are members of the immunoglobulin (Ig) superfamily, containing an Ig variable-region-like N-terminal domain followed by a varying number of Ig constant-region-like domains exposed at the cell surface (21,22).…”

CEACAM1 Dynamics during Neisseria gonorrhoeae Suppression of CD4+ T Lymphocyte Activation

“…Moreover, when combined with their phenomenal ability to alter its surface structures (41), their subversion of CEACAM1 coinhibitory function suggests that the bacteria persist by stealth, both escaping and actively suppressing the adaptive immune response. Considering that other human restricted-pathogens including Neisseria meningitidis (16), Haemophilus influenzae (57), and Moraxella catarrhalis (58), each bind CEACAM1, it is enticing to speculate that these pathogens also share this effective evolutionary strategy.…”

Two Variable Regions in Carcinoembryonic Antigen-related Cell Adhesion Molecule1 N-terminal Domains Located in or Next to Monoclonal Antibody and Adhesion Epitopes Show Evidence of Recombination in Rat but Not in Human

“…Further analysis with variants of peptide 9.2 containing C-and N-terminal deletions (Table III) defined the adhesion epitope for rat CEACAM1 to be PDSEIARYIRS, a sequence encompassing the entire CЈ ␤-strand and part of (33) hCEACAM1 (28), and the docking sites for MHV (57)(58)(59) and opa proteins (81,82) are located primarily in the C ␤-strand and the CCЈ loop domain (Fig. 2B).…”