Immune Recognition

L.J. Beamer, S.F. Carroll, D. Eisenberg	The Crystal Structure of BPI, the Human Bactericidal/Permeability - Increasing Protein	A
B. Gigant, J-B. Charbonnier, Z. Eshhar, B.S. Green, M. Knossow	Structure, Mechanism and Specificity of a Catalytic Antibody	A
M. Gajhede, O. Mirza, H. Ipsen, J.N. Larsen, M.D. Spangfort	Understanding IgE allergen epitopes: Complex formation between a Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen bet v 1	A
L. Wyns	Single Domain Camelid Antibodies: Structures of Antigen Complexes and their Use as Inhibitors and Substrate Mimics	A
E. Hewat	Virus-Antibody Interactions Visualized by Combining Cryo-Electron Microscopy and X-Ray Data	A
D. Housset, G. Mazza, C. Gregoirem C. Piras, B. Malissen, J-C Fontecilla-Camps	The Crystal Structure of KB5-C20 scFv TCR/ Désiré-1 Fab Complex	A
K. Fütterer, R.A. Grucza, A.C. Chan, G. Waksman	Molecular Basis for SYK Signalling Revealed by Its Tandem SH2 Domain/Itam Bound Structure	A

Presentations given during the “ Immune Recognition ” session concerned mainly the acquired immune response (antibodies and T cell receptors), but also included the innate immune response and signal transduction in lymphocytes. Lesa Beamer (University of Missouri) described the structure of human Bactericidal/Permeability Increasing Protein (BPI) found in polymorphonuclear neutrophils. This protein neutralises the strong inflammatory response induced by LPS from gram-negative bacteria. The crystal structure revealed two bound molecules of phosphatidylcholine, suggesting the mode of interaction of BPI with the lipid moiety of LPS in this example of innate immune recognition. The vast antigen-binding repertoire of antibodies can be harnessed to produce immunoglobulins with specific catalytic properties. Benoît Gigant (Laboratoire d’Enzymologie et Biochimie Structurales, Gif sur Yvette) presented structural data on such an antibody which catalyses hydrolysis of p-nitrophenyl and p-nitrobenzyl esters. The crystal structures of Fab complexes with transition state analogues of these two types of ester provide an explanation of the relative difference in hydrolysis rates by the catalytic antibody. In order to characterise the antigenic determinants of birch tree pollen, Micheal Gajhede (University of Copenhagen) presented results from a study of the Bet v 1 allergen complexed to the Fab fragment of a monoclonal antibody. This showed the epitope to be one of three determinants found in prior studies that are also present in homologous tree pollen allergens. Camelid antibodies present a curiosity in immunoglobulin structure since they are composed of heavy chains only - the antigen-binding site is thus formed by a single variable domain. The structure of the complex formed between the VH domain of a camelid antibody and lysozyme, presented by Lode Wyns (Vrije Universiteit Brussel) showed that the unusual arrangement of CDR1 and CDR3 created an antigen-binding site that could readily insert into the substrate-binding site of lysozyme. The use of both X-ray crystallography and electron microscopy, combining high and low resolution studies, was discussed by Elisabeth Hewat (Jean-Pierre Ebel Institut de Biologie Structurale, Grenoble). Examples were presented to illustrate how neutralising anti-viral antibodies can function either by blocking the host receptor-binding site (Foot and Mouth Disease Virus) or by possible impairment of dissociation of the virus (Rhinovirus). Although the fold of the T cell receptor (TCR) is very similar to that of antibodies, there are still very few structural determinations of this antigenic receptor. Dominique Housset (Jean-Pierre Ebel Institut de Biologie Structurale, Grenoble) described the structure of a Fv fragment of a TCR bound by the Fab fragment of a clonotypic monoclonal antibody, revealing a new fold for the Vb domain. Protein tyrosine kinases have an essential role in signal transduction following engagement of antigen by receptors on the surface of lymphocytes. Klaus Fütterer (Washington University School of Medicine, Saint Louis) described how the conformational flexibility and structural independence of the two SH2 domains, shown in the crystal structure of Syk (homologous to ZAP-70) complexed to ITAM peptide ligands, could account for the exploitation of this tyrosine kinase in several different immune (and non-immune) signal transduction pathways.