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Self-Association of an Activating Natural Killer Cell Receptor, KIR2DS1 1 1 1,2 Michael Hayley , Sarah Bourbigot , Valerie Booth * 1 Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada, 2 Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada Abstract As a major component of the innate immune system, natural killer cells are responsible for activating the cytolytic killing of certain pathogen-infected or tumor cells. The self-recognition of natural killer cells is achieved in part by the killer cell immunoglobulin-like receptors (KIRs) protein family. In the current study, using a suite of biophysical methods, we investigate the self-association of an activating KIR, KIR2DS1. This KIR is of particular interest because when in the presence of the HLA-Cw6 protein, KIR2DS1 becomes a major risk factor for psoriasis, an autoimmune chronic skin disease. Using circular dichroism spectroscopy, dynamic light scattering, and atomic force microscopy, we reveal that KIR2DS1 self- associates in a well-defined fashion. Our novel results on an activating KIR allow us to suggest a working model for the KIR2DS1- HLA class I molecular mechanism. Citation: Hayley M, Bourbigot S, Booth V (2011) Self-Association of an Activating Natural Killer Cell Receptor, KIR2DS1. PLoS ONE 6(8): e23052. doi:10.1371/ journal.pone.0023052 ´ ´ Editor: Jacques Zimmer, Centre de Recherche Public de la Sante (CRP-Sante), Luxembourg Received June 17, 2011; Accepted July 5, 2011; Published August 30, 2011 Copyright: 2011 Hayley