title: A Linear Epitope in the N-Terminal Domain of CCR5 and Its Interaction with Antibody.
abstract: The CCR5 receptor plays a role in several key physiological and pathological processes and is an important therapeutic target. Inhibition of the CCR5 axis by passive or active immunisation offers one very selective strategy for intervention. In this study we define a new linear epitope within the extracellular domain of CCR5 recognised by two independently produced monoclonal antibodies. A short peptide encoding the linear epitope can induce antibodies which recognise the intact receptor when administered colinear with a tetanus toxoid helper T cell epitope. The monoclonal antibody RoAb 13 is shown to bind to both cells and peptide with moderate to high affinity (6x10^8 and 1.2x107 M-1 respectively), and binding to the peptide is enhanced by sulfation of tyrosines at positions 10 and 14. RoAb13, which has previously been shown to block HIV infection, also blocks migration of monocytes in response to CCR5 binding chemokines and to inflammatory macrophage conditioned medium. A Fab fragment of RoAb13 has been crystallised and a structure of the antibody is reported to 2.1 angstrom resolution.
authors.affiliation: Division of Infection and Immunity, UCL, Gower St., London, United Kingdom.
authors.forename: Benny
authors.initials: B
authors.lastname: Chain
authors.affiliation: Division of Infection and Immunity, UCL, Gower St., London, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Arnold
authors.affiliation: Division of Infection and Immunity, UCL, Gower St., London, United Kingdom.
authors.forename: Samia
authors.initials: S
authors.lastname: Akthar
authors.affiliation: Virology Discovery and Translational Area, Roche Nutley, 340 Kingsland Street Nutley, NJ 07110, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Brandt
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Davis
authors.affiliation: Division of Infection and Immunity, UCL, Gower St., London, United Kingdom.
authors.forename: Mahdad
authors.initials: M
authors.lastname: Noursadeghi
authors.affiliation: Division of Infection and Immunity, UCL, Gower St., London, United Kingdom.
authors.forename: Thabo
authors.initials: T
authors.lastname: Lapp
authors.affiliation: Virology Discovery and Translational Area, Roche Nutley, 340 Kingsland Street Nutley, NJ 07110, United States of America.
authors.forename: Changhua
authors.initials: C
authors.lastname: Ji
authors.affiliation: Virology Discovery and Translational Area, Roche Nutley, 340 Kingsland Street Nutley, NJ 07110, United States of America.
authors.forename: Surya
authors.initials: S
authors.lastname: Sankuratri
authors.affiliation: Division of Infection and Immunity, UCL, Gower St., London, United Kingdom.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Lata
authors.initials: L
authors.lastname: Govada
authors.affiliation: Laboratory of Structural and Supramolecular Chemistry, Department of Physical Chemistry, National Centre for Scientific Research 'Demokritos', Athens, Greece.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Saridakis
authors.affiliation: Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Naomi
authors.initials: N
authors.lastname: Chayen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D016466:CHO Cells; D002633:Chemotaxis; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000737:chemistry* / Q000276:immunology*; D013045:Species Specificity
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D008024:Ligands; D019713:Receptors, CCR5