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A Conserved Host and Pathogen Recognition Site on Immunoglobulins: Structural and Functional Aspects

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Current Topics in Innate Immunity II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 946))

Abstract

A common site in the constant region (Fc) of immunoglobulins is recognized by host receptors and is a frequent target of proteins expressed by pathogens. This site is located at the junction of two constant domains in the antibody heavy chains and produces a large shallow cavity formed by loops of the CH2 and CH3 domains in IgG and IgA (CH3 and CH4 domains in IgM). Crystal structures have been determined for complexes of IgG-Fc and IgA-Fc with a structurally diverse set of host, pathogen and in vitro selected ligands. While pathogen proteins may directly block interactions with the immunoglobulins thereby evading host immunity, it is likely that the same pathogen molecules also interact with other host factors to carry out their primary biological function. Herein we review the structural and functional aspects of host and pathogen molecular recognition of the common site on the Fc of immunoglobulins. We also propose that some pathogen proteins may promote virulence by affecting the bridging between innate and adaptive immunity.

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Acknowledgments

This work was funded by grant ID543317 (to PAR and BDW) from the National Health and Medical Research Council of Australia (NHMRC). PAR was a recipient of an RD Wright CDA (ID365209) from the NHMRC. JT was supported by the MRC and the Wellcome Trust with partial support from the NIHR Cambridge Biomedical Research Centre. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute.

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Authors and Affiliations

  1. Centre for Immunology, Burnet Institute, 3004, Melbourne, VIC, Australia

    Bruce D. Wines, Halina M. Trist, William Farrugia, Chloe Ngo & Paul A. Ramsland

  2. Department of Pathology, University of Melbourne, 3010, Melbourne, VIC, Australia

    Bruce D. Wines & Chloe Ngo

  3. Department of Immunology, Monash University, 3004, Melbourne, VIC, Australia

    Bruce D. Wines & Paul A. Ramsland

  4. Department of Pathology, Immunology Division, Cambridge Institute for Medical Research, University of Cambridge, CB2 0XY, Cambridge, UK

    John Trowsdale

  5. Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, 22362, Lund, Sölvegatan 23, Sweden

    Thomas Areschoug & Gunnar Lindahl

  6. School of Medical Sciences and Maurice Wilkins Centre of Excellence, University of Auckland, 1020, Auckland, New Zealand

    John D. Fraser

  7. Centre for Immunology, Burnet Institute, VIC 3004, Melbourne, Australia

    Paul A. Ramsland

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  1. Department Of Pathology Laboratory Of, Medicine, University Of Pennsylvania, Johnson Pavilion 410, Philadelphia, 19104, Pennsylvania, USA

    John D. Lambris

  2. Health Sciences Center, University of Louisville, Louisville, 40292, Kentucky, USA

    George Hajishengallis

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Wines, B.D. et al. (2012). A Conserved Host and Pathogen Recognition Site on Immunoglobulins: Structural and Functional Aspects. In: Lambris, J., Hajishengallis, G. (eds) Current Topics in Innate Immunity II. Advances in Experimental Medicine and Biology, vol 946. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0106-3_6

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