• Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1

      O'Connor, Geraldine M.; Vivian, Julian P.; Gostick, Emma; Pymm, Phillip; Lafont, Bernard A.; Price, David A.; Rossjohn, Jamie; Brooks, Andrew G.; McVicar, Daniel W.; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, Wales, United Kingdom. Non-Human Primate Immunogenetics and Cellular Immunology Unit, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, Wales, United Kingdom Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, Wales, United Kingdom. Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia. (American Society for Microbiology, 2015-04-21)
      Killer cell immunoglobulin-like receptors (KIRs) play an important role in the activation of natural killer (NK) cells, which in turn contribute to the effective immune control of many viral infections. In the context of HIV infection, the closely related KIR3DL1 and KIR3DS1 molecules, in particular, have been associated with disease outcome. Inhibitory signals via KIR3DL1 are disrupted by downregulation of HLA class I ligands on the infected cell surface and can also be impacted by changes in the presented peptide repertoire. In contrast, the activatory ligands for KIR3DS1 remain obscure. We used a structure-driven approach to define the characteristics of HLA class I-restricted peptides that interact with KIR3DL1 and KIR3DS1. In the case of HLAB*57:01, we used this knowledge to identify bona fide HIV-derived peptide epitopes with similar properties. Two such peptides facilitated productive interactions between HLA-B*57:01 and KIR3DS1. These data reveal the presence of KIR3DS1 ligands within the HIV-specific peptide repertoire presented by a protective HLA class I allotype, thereby enhancing our mechanistic understanding of the processes that enable NK cells to impact disease outcome.
    • Use of pulsed-field gel electrophoresis and flagellin gene typing in identifying clonal groups of campylobacter jejuni and campylobacter coli in farm and clinical environments

      Fitzgerald, Collette; Stanley, Karen; Andrew, Sarah M.; Jones, Keith; Lancaster University (American Society for Microbiology, 2001-04-01)
      Although campylobacters have been isolated from a wide range of animal hosts, the association between campylobacters isolated from humans and animals in the farm environment is unclear. Flagellin gene typing and pulsed-field gel electrophoresis (PFGE) was used to investigate the genetic diversity among isolates from animals (cattle, sheep, and turkey) in farm environments and sporadic cases of campylobacteriosis in the same geographical area. Forty-eight combined fla types were seen among the 315 Campylobacter isolates studied. Six were found in isolates from all four hosts and represented 50% of the total number of isolates. Seventy-one different SmaI PFGE macrorestriction profiles (mrps) were observed, with 86% of isolates assigned to one of 29 different mrps. Fifty-seven isolates from diverse hosts, times, and sources had an identical SmaI mrp and combined fla type. Conversely, a number of genotypes were unique to a particular host. Molecular evidence is provided which suggests a link between campylobacters in the farm environment with those causing disease in the community.