N255 is a key residue for recognition by a monoclonal antibody which protects against Yersinia pestis infection

• DOI: 10.1016/j.vaccine.2009.09.061
• Publication Date: 2009-09-27T08:09:42Z
• Authors: Jim Hill; Sophie Leary; Sophie Smither; Angus Best; Jonas Pettersson; Ake Forsberg; Bry Lingard; Alexandria Lipka; Katherine A. Brown; E. Diane Williamson; Richard W. Titball
• Keywords: Pore Forming Cytotoxic Proteins; 0301 basic medicine; Antigens, Bacterial; Mice, Inbred BALB C; Plague; Plague Vaccine; Yersinia pestis; Molecular Sequence Data; Antibody Affinity; Antibodies, Monoclonal; Antibodies, Bacterial; Recombinant Proteins; Cell Line; Protein Structure, Tertiary; 3. Good health; Epitopes; Mice; 03 medical and health sciences; Mutagenesis, Site-Directed; Animals; Amino Acid Sequence

Mab7.3 to Yersinia pestis LcrV antigen (LcrV(Ype)) protected J774A.1 macrophages in vitro from killing by a Yersinia pseudotuberculosis strain expressing LcrV(Ype). Of 4 site-directed mutations in the coiled-coil region (148-169) and 7 mutations in the 225-255 sequence of LcrV(Ype), only the mutation of N255 to D255, abrogated the binding of Mab7.3 and reduced its protective capacity against plague. Since the Mab7.3 epitope in LcrV(Ype) (135-275) encompasses a region (136-180) thought to be exposed on the injectisome, we suggest that Mab7.3 protects by binding to LcrV(Ype) and interfering with protein-protein interactions necessary for type three secretion.