ferences in response to different amino acid substitutions were apparent. One consistency between all species and strains tested was the dramatic loss of binding following I91A substitution which, as observed previously, appears to be central in an overlapping bacterial binding footprint on CEACAM1 (Virji et al., 1999; . A similar situation occurs on the mouse CEACAM1a (MHVR1a) N-terminal domain, in which Ile-41 appears to engage with the mouse hepatitis virus spike protein. Replacement of Ile-41 by Thr in the MHVR1b allele reduces virus binding significantly (Tan et al., 2002) . Cell surface receptor interactions with their ligands often involve hydrophobic contact points which provides the major binding energy. Hydrophobic residues surrounding these contribute to the specificity of binding (Clackson and Wells, 1995; Kwong et al., 1998; Kim et al., 2001) . Thus in murine CEACAM1, the protruding Ile-41, which is surrounded by a number of surface exposed charged residues, e.g. Asp-42, Glu-44, Arg-47, Asp89, Glu-93 and Arg-97, might form such a binding area (Tan et al., 2002) . Accordingly from current studies also, mutations introduced at position 91 in the human receptor support the requirement for a hydrophobic pocket at this site. In addition, an extended aliphatic chain is preferred as Ala disrupted binding of all bacteria and the polar Thr reduced binding of all Hi and several Nm strains. Only I91L was more frequently tolerated. This binding pocket is flanked by several polar residues (Fig. 1 ) whose contribution to bacterial ligand binding is apparent and variable (Virji et al., 1999; . The importance of the Ile-91 and the surrounding residues on human CEACAM1 in bacterial binding is also supported by the observation that the mAb YTH71.3 directed against the N-domain also requires several residues in common with bacteria and blocks binding of all CEACAM1-binding bacteria we have investigated (Virji et al., 1999; Hill and Virji, 2003) .