Monoclonal antibodies to Escherichia coli heat-labile enterotoxins: neutralising activity and differentiation of human and porcine LTs and cholera toxin.

Abstract

Forty-four monoclonal antibodies (MAbs) prepared against heat-labile enterotoxins (LTs) from human (LTh) or porcine (LTp) E. coli isolates were characterised, especially with regard to their reactivity with epitopes shared with the heterologous LT and/or cholera toxin (CT), and their toxin neutralising activity. Of 24 MAbs against LTh (all directed against the B subunit portion) 12 cross-reacted with LTp and CT, 4 with LTp but not CT, and 1 with CT but not LTp; 7 MAbs reacted with LTh epitope(s) not shared by either LTp or CT. Among 20 MAbs against LTp (9 directed against the B subunits and 11 against the A subunit) 2 cross-reacted with LTh as well as CT, 13 with LTh but not CT, and 5 MAbs were specific for LTp. Irrespective of whether the anti-LT MAbs were directed against shared or unshared epitopes, or against the A or B subunits, they neutralised their homologous toxin in direct proportion to their toxin-binding titre. The results show how minute differences in enterotoxin primary structures e.g., the LTh and LTp B chains differ in only 4 of 103 amino acid residues, are associated with antigenic epitopes against which toxin-differentiating MAbs with neutralising activity can be produced. Such MAbs are promising tools for species-specific diagnostic detection of enterotoxins in clinical specimens.