• In vitro cyto-toxic assessment of heavy metals and their binary mixtures on mast cell-like, rat basophilic leukemia (RBL-2H3) cells

      Eze, Chukwuebuka T.; Michelangeli, Francesco; Otitoloju, Adebayo A.; University of Chester, University of Lagos, Nigeria, Federal University Oye-Ekiti, Nigeria (Elsevier, 2019-02-11)
      We investigated the cytotoxicity and mechanisms of cell death induced by salts of Cadmium (Cd2+), Lead (Pb2+), Arsenic (AsO4 3−) and Chromium (Cr+6) on RBL-2H3 cells (a model mast cell line). In addition, cyto-toxic effect on cell viability was assessed to reveal their nature of interaction in binary mixture. The individual cytotoxic characteristics of these metals on RBL-2H3 cell viability showed a concentration- dependent reduction of cell viability. We observed that concentration-dependent cytotoxic potency on RBL-2H3 cells of these metals range in the following order Cd2+>Cr+6>As O4 3−>Pb2+ with LC50 values of 0.11 μM, 93.58 μM, 397.9 μM and 485.3 μM respectively. Additive effects were observed with Pb2+ + Cd2+, Pb2+ + AsO4 3−, Pb2+ + Cr+6 and AsO4 3− + Cr+6. The study revealed that Pb2+, Cd2+, AsO4 3− and Cr+6 could induce significant (P<0.01) cell death by apoptosis in RBL-2H3. Highly significant necrotic cell death was observed with Pb2+ and Cr+6 (P<0.01) than Cd2+ and AsO4 3− (P<0.05). Overall, it can be deduced that several cell death executing pathways may be concomitantly activated on exposure to heavy metals and the predominance of one over others might depend on the type of heavy metal, concentration and the metabolic state of the cell. Eventually, binary mixtures of some of these metals showed less cytotoxicity than would be expected from their individual actions and may depend on the co-exposure of the metal ions and their modes of action.
    • Increased circulating Dickkopf-1 in Paget's disease of bone

      Marshall, Michael J.; Evans, Sally F.; Sharp, Christopher A.; Powell, Diane E.; McCarthy, Helen S.; Davie, Michael W. J.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry / University of Chester ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry (Elsevier, 2009-07)
      This article discusses Dickkopf-1 (Dkk-1), which is a secreted inhibitor of Wnt signaling which in adults regulates bone turnover. Dkk-1 over-production is implicated in osteolytic disease where it inhibits bone formation and stimulates bone breakdown. Recently it was reported that osteoblastic cells from Paget's disease of bone (PDB) over-expressed Dkk-1. This study aimed yo see if increased Dkk-1 was detected in serum from patients with PDB. The results showed that Dkk-1 and total serum alkaline phosphatase activity (tsAP) were significantly elevated in sera from PDB patients. Patients with polyostotic PDB had significantly higher levels of tsAP but not Dkk-1, than monostotic patients. TsAP but not Dkk-1, was significantly lower in sera from bisphosphonate treated versus untreated PDB patients. Dkk-1 and tsAP were not significantly correlated. Dkk-1 may be a useful biomarker of PDB and the authors speculate that Dkk-1 may play a central role in the etiology of PDB.
    • Individual, social, and environmental factors affecting salivary and fecal cortisol levels in captive pied tamarins (Saguinus bicolor)

      Wormell, Dominic; Smith, Tessa E.; Price, Eluned E.; Ahsmann, J.; Glendewar, G.; Hunt, J.; Coleman, Robert, C.; University of Chester (Wiley, 2019-08-01)
      Pied tamarins (Saguinus bicolor) are endangered New World primates, and in captivity appear to be very susceptible to stress. We measured cortisol in 214 saliva samples from 36 tamarins and in 227 fecal samples from 27 tamarins, and investigated the effects of age, sex, pregnancy, rearing history, social status, weight, group composition, and enclosure type using generalized linear mixed models. There was no effect of age on either fecal or salivary cortisol levels. Female pied tamarins in late pregnancy had higher fecal cortisol levels than those in early pregnancy, or nonpregnant females, but there was no effect of pregnancy on salivary cortisol. Females had higher salivary cortisol levels than males, but there was no effect of rearing history. However, for fecal cortisol, there was an interaction between sex and rearing history. Hand‐reared tamarins overall had higher fecal cortisol levels, but while male parent‐reared tamarins had higher levels than females who were parent‐ reared, the reverse was true for hand‐reared individuals. There was a trend towards lower fecal cortisol levels in subordinate individuals, but no effect of status on salivary cortisol. Fecal but not salivary cortisol levels declined with increasing weight. We found little effect of group composition on cortisol levels in either saliva or feces, suggesting that as long as tamarins are housed socially, the nature of the group is of less importance. However, animals in off‐show enclosures had higher salivary and fecal cortisol levels than individuals housed on‐show. We suggest that large on‐show enclosures with permanent access to off‐exhibit areas may compensate for the effects of visitor disturbance, and a larger number of tamarins of the same species housed close together may explain the higher cortisol levels found in tamarins living in off‐show accommodation, but further research is needed.
    • Influence of environmental factors on the growth and interactions between salt marsh plants: Effects of salinity, sediment and waterlogging

      Huckle, Jonathan M.; Potter, Jacqueline; Marrs, Robert H.; University College Chester ; University College Chester ; University of Liverpool (British Ecological Society, 2009-07-21)
      Artificial environmental gradients were established in a series of pot experiments to investigate the effect of salinity, sediment type and waterlogging on the growth, and interactions between Spartina anglica and Puccinellia maritima. In each experiment, one environmental variable was manipulated and plants grown in pairwise combinations to examine the effect of the environmental factor on the intensity of intra- and interspecific interactions, quantified using the Relative Neighbour Effect (RNE) index. 2 Puccinellia was found to exert an asymmetric, one-way competitive dominance above ground over Spartina in experiments where gradients of sediment type and waterlogging were established. The intensity of the competition was highest in conditions with the least abiotic stress and lower or non-existent where stress was increased. 3 The intensity of the above-ground competition was greatest in loam and least in sand sediments. Reduction in competitive intensity in sand was accompanied by an increase in below-ground Spartina biomass and it is suggested that the production of rhizomes is a potential mechanism by which this species can expand vegetatively into areas without competition. 4 Interspecific competition on Spartina from Puccinellia also varied in intensity in the waterlogging experiment, being more intense in non-immersed treatments, where abiotic stress was reduced. 5 The competitive dominance of Puccinellia and the competition avoidance mechanism shown by Spartina in these experiments help to explain the successional interactions between the species along environmental gradients in natural salt marsh communities.
    • The inhibition of osteoprotegerin production in human osteoblast-like cells by dissociated glucocorticoid analoges

      Humphrey, E. L.; Smith, Heather L.; Williams, John H. H.; Marshall, Michael J.; University College Chester (Williams) (American Society for Bone and Mineral Research, 2004-06)
    • Integrating role-play with case study and carbon footprint monitoring: A transformative approach to enhancing learners' behaviour for a more sustainable environment

      Oliver, Simon P.; University of Chester (Look Acedemic Publishers, 2016-05-01)
      Educators have long used role-play to encourage a significant shift in learner perspective, and the social and cognitive benefits of this active learning tool are well documented. Although the use of role-play has been encouraged as a transformative approach to challenge the worldview of individual learners in the context of environmental education, the efficacy of its application as a direct means to enhance learners’ behavior towards the environment has not been previously investigated. In this study role-play simulations were integrated with case study to expose learners to some of the socioscientific issues that typically arise from environmental debate. Learners were separated into groups representing the interests of parties that typically negotiate environmental affairs in real world scenarios (conservationists, scientists, politicians, NGOs, stakeholders), and tasked with preparing role-play simulations using a variety of flipped learning techniques. Learners’ carbon footprints were monitored pre and post intervention, and CO2 emission scores were used as a proxy for their behaviour towards the environment. Five role-play simulations were run overall. These were integrated with case studies associated with fisheries issues, and climate change. Anonymous participant surveys indicated that learners responded positively to the intervention, and participants’ CO2 emission scores improved significantly (T1,59 = 2.723, p = 0.009). In the context of environmental sciences, learners that engage in the integrated role-play and case study approach may benefit from flipped learning techniques to prepare their simulations, and gain confidence from self-actualising moments of achievement when they realise an improvement in their environmental behaviour.
    • Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells

      Townsley, Elizabeth; O'Connor, Geraldine M.; Cosgrove, Cormac; Woda, Marcia; Co, Mary; Thomas, Stephen J.; Kalayanarooj, Siripen; Yoon, In-Kyu; Nisalak, Ananda; Srikiatkhachorn, Anon; et al. (2015-10-06)
      Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR-HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56(dim) NK cells, which are known to express KIRs. Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57(+) subjects with acute DENV infection revealed marked activation of NS1 tetramer-binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR-HLA interactions in the modulation of disease outcomes.
    • The interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitope

      Saunders, Philippa M.; Vivian, Julian P.; Baschuk, Nikola; Beddoe, Travis; Widjaja, Jacqueline M.; O’Connor, Geraldine M.; Hitchen, Corinne; Pymm, Phillip; Andrews, Daniel M.; Gras, Stephanie; et al. (2015-01-02)
      The killer cell Ig-like receptor 3DL1 (KIR3DL1) inhibits activation of NK cells upon interaction with HLA class I molecules such as HLA-B*57:01, which contains the Bw4 epitope spanning residues 77-83 (e.g., NLRIALR), and not with HLA allomorphs that possess the Bw6 motif (e.g., HLA-B*08:01), which differ at residues 77, 80, 81, 82, and 83. Although Bw4 residues Ile(80) and Arg(83) directly interact with KIR3DL1*001, their precise role in determining KIR3DL1-HLA-Bw4 specificity remains unclear. Recognition of HLA-B*57:01 by either KIR3DL1(+) NK cells or the NK cell line YTS transfected with KIR3DL1*001 was impaired by mutation of residues 80 and 83 of HLA-B*57:01 to the corresponding amino acids within the Bw6 motif. Conversely, the simultaneous introduction of three Bw4 residues at positions 80, 82, and 83 into HLA-B*08:01 conferred an interaction with KIR3DL1*001. Structural analysis of HLA-B*57:01, HLA-B*08:01, and mutants of each bearing substitutions at positions 80 and 83 revealed that Ile(80) and Arg(83) within the Bw4 motif constrain the conformation of Glu(76), primarily through a salt bridge between Arg(83) and Glu(76). This salt bridge was absent in HLA-Bw6 molecules as well as position 83 mutants of HLA-B*57:01. Mutation of the Bw4 residue Ile(80) also disrupted this salt bridge, providing further insight into the role that position 80 plays in mediating KIR3DL1 recognition. Thus, the strict conformation of HLA-Bw4 allotypes, held in place by the Glu(76)-Arg(83) interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the alpha1 helix that is less permissive for KIR3DL1 binding.
    • Interleukin-1 beta blocks glucocorticoid inhibition of osteoprotegerin production in osteoblastic cells

      Humphrey, E. L.; Smith, Heather L.; Williams, John H. H.; Marshall, Michael J.; University College Chester (Williams) (American Society for Bone and Mineral Research, 2004-06)
    • Interleukin-17 Expression in the Barrett’s Metaplasia-Dysplasia-Adenocarcinoma Sequence

      Bannister, Jim R.; Khan, Abdul L.; Eccleston, David W.; Deol-Poonia, Ranjeev K.; Hughes, Stephen F.; University of Chester; Aintree University Hospital (Hindawi Publishing Corporation, 2012-12-30)
      Introduction. This pilot study evaluated the expression of the proinflammatory cytokine IL-17 along the Barrett’s metaplasia-dysplasia-adenocarcinoma sequence by establishing the expression levels of IL-17 in columnar epithelium, intestinal metaplastic cells, and dysplastic/glandular neoplastic cells. Immunohistochemical techniques were used to examine the accumulation of the proinflammatory cytokine IL-17 in forty () formalin-fixed, paraffin-embedded oesophageal archived specimens across a range of endoscopic diagnostic categories, and a highly significant difference was found, where , in IL-17 expression (Kruskall Wallis and Mann-Whitney ) between all the cell types examined. There was also a strong positive correlation (Spearman's rank correlation) between disease progression and IL-17 expression (, , ), IL-17 expression was absent or absent/weak in columnar epithelium, weak to moderate in columnar metaplastic cells, and moderate to strong in dysplastic/neoplastic cells, which demonstrated that the elevation of IL-17 expression occurs in the progression of the disease. Understanding the differential expression of IL-17 between benign and malignant tissue potentially has a significant diagnostic, prognostic, and therapeutic value. Ultimately, this selective biomarker may be employed in routine clinical practice for the screening of oesophageal adenocarcinoma.
    • Interpreting predictive maps of disease, highlighting the pitfalls of species distribution models in epidemiology

      Wardrop, Nicola A.; Geary, Matthew; Osborne, Patrick E.; Atkinson, Peter M.; University of Southampton ; University of Chester / University of Southampton ; University of Southampton ; University of Southampton (University of Naples, 2014-11-01)
      The application of spatial modelling to epidemiology has increased significantly over the past decade, delivering enhanced understanding of the environmental and climatic factors affecting disease distributions and providing spatially continuous representations of disease risk (predictive maps). These outputs provide significant information for disease control programmes, allowing spatial targeting and tailored interventions. However, several factors (e.g. sampling protocols or temporal disease spread) can influence predictive mapping outputs. This paper proposes a conceptual framework which defines several scenarios and their potential impact on resulting predictive outputs, using simulated data to provide an exemplar. It is vital that researchers recognise these scenarios and their influence on predictive models and their outputs, as a failure to do so may lead to inaccurate interpretation of predictive maps. As long as these considerations are kept in mind, predictive mapping will continue to contribute significantly to epidemiological research and disease control planning.
    • Interspecific and intraspecific interactions between salt marsh plants: Integrating the effects of environmental factors and density on plant performance

      Huckle, Jonathan M.; Marrs, Robert H.; Potter, Jacqueline; University of Liverpool ; University of Liverpool ; Chester College of Higher Education (Nordic Ecological Society, 2002-02)
      There has been much debate about the role of plant interactions in the structure and function of vegetation communities. Here the results of a pot experiment with controlled environments are described where three environmental variables (nutrients, sediment type and waterlogging) were manipulated factorially to identify their effects on the growth and intensity of interactions occurring between Spartina anglica and Puccinellia maritima. The two species were grown in split-plot planting treatments, representing intraspecific and interspecific addition series experiments, to determine individual and interactive effects of environmental factors and plant interactions on plant biomass. Above-ground growth of both species involved interactions between the environmental and planting treatments, while below-ground, environmental factors affected the biomass irrespective of planting treatments. It was suggested that this difference in growth response is evidence that in our experiment plant interactions between the two species occur primarily at the above-ground level. The intensity of plant interactions varied in a number of ways. First, interactions between Spartina and Puccinellia were distinctly asymmetrical, Puccinellia exerting a competitive effect on Spartina, with no reciprocal effect, and with a facilitative effect of Spartina on Puccinellia in low nutrient conditions. Second, the interactions varied in intensity in different environmental conditions. Interspecific competitive effects of Puccinellia on Spartina were more intense in conditions favourable to growth of Puccinellia and reduced or non-existent in environments with more abiotic stress. Third, intraspecific competition was found to be less intense for both species than interspecific interactions. Finally, the intensity of plant interactions involving both species was more intense above ground than below ground, with a disproportionate reduction in the intensity of interspecific competition below relative to above ground in treatments with less productive sediments and greater immersion. This is interpreted as reflecting a potential mechanism by which Spartina may be able to evade competitive neighbours.
    • An introduction to Phylogenetic Path Analysis

      Gonzalez-Voyer, A.; von Hardenberg, Achaz; Estación Biológica de Doñana, Gran Paradiso National Park (Springer Verlag, 2014)
      The questions addressed by macroevolutionary biologists are often impervious to experimental approaches, and alternative methods have to be adopted. The phy- logenetic comparative approach is a very powerful one since it combines a large number of species and thus spans long periods of evolutionary change. However, there are limits to the inferences that can be drawn from the results, in part due to the limitations of the most commonly employed analytical methods. In this chapter, we show how confirmatory path analysis can be undertaken explicitly controlling for non-independence due to shared ancestry. The phylogenetic path analysis method we present allows researchers to move beyond the estimation of direct effects and analyze the relative importance of alternative causal models including direct and indirect paths of influence among variables. We begin the chapter with a general introduction to path analysis and then present a step-by-step guide to phylogenetic path analysis using the d-separation method. We also show how the known statistical problems associated with non-independence of data points due to shared ancestry become compounded in path analysis. We finish with a discussion about the potential effects of collinearity and measurement error, and a look toward possible future developments.
    • An investigation into the numerical determinants of secondary sex ratio

      Lewis, Stephen J.; Glenn, Janine; Chester College of Higher Education (2000)
      Data from the North Wales parishes of Hawarden and Northop were found previously to show seasonality for birth rate. In keeping with values reported in other studies, the annual secondary sex ratio of 105.3% was found. This sex ratio was also found to vary throughout the year in a cyclical way with a peak occuring in late summer. When male and female birth rates were investigated separately, it was found that females showed a more pronounced cyclicity than males with the peaks for both sexes occuring in the spring. A significant negative correlation between sex ratio at birth and mean day lenght (hours between sunrise and sunset) of the putative month of conception was observed. Sex ratio is a useful but derived parameter and has no independant existence upon which natural selection can be said to exert a direct influence. Therefore, the behaviour of the determinants of sex ratio should not be overlooked.
    • An investigation to determine the nutritional adequacy and individuals experience of a very low fat diet used to treat type V hypertriglyceridaemia

      Whitfield-Brown, Louisa M.; Hamer, O.; Ellahi, Basma; Burden, Sorrel; Durrington, Paul; University of Chester ; Manchester Royal Infirmary ; University of Chester ; Manchester Royal Infirmary ; University of Manchester (Wiley, 2009-05-15)
      This article discusses a study of eight patients with type V hypertriglyceridaemia on a low fat diet. The nutritional adequact of the diet and the barriers and enablers to adherence were analysed.
    • Involvement of recreational anglers in the eradication of alien brook trout from high altitude lakes

      Tiberti, Rocco; Ottino, Michelle; Brighenti, Stefano; Iacobuzio, Rocco; Rolla, Matteo; von Hardenberg, Achaz; Bassano, Bruno; Gran Paradiso National Park, University of Pavia, Università degli studi di Trento, Fondazione E. Mach, Università degli Studi di Milano, Swansea University, University of Chester (Gran Paradiso National Park Agency, 2017)
      Stocking programmes for recreational angling are primarily responsible for the spread and ecological impact of introduced sh in high-altitude, originally shless lakes. In 2013, the Gran Paradiso National Park started an eradication campaign of brook trout by intensive gill-netting. Local anglers were invited to attend two angling sessions to start the eradication before gill-netting in an experimental lake, as part of an education action devoted to these critical stakeholders. The angling sessions turned out to be a valuable help for the eradication campaign and the aim of this study is to report on the outcomes of these angling sessions. Angling techniques were highly size-selective, removing a substantial part of the adult population and of the sh biomass, but their contribution to the eradication of small sh (<15cm) was irrelevant. Therefore, angling cannot completely eradicate age-structured populations. However, there is scope to use angling sessions as a support for eradication campaigns and as an emergency measure for recent sh introduc- tions. Similar actions should be considered whenever a sh eradication programme is planned. These ndings, however, do not imply a general endorsement for angling within protected areas.
    • Is cortisol a reliable indicator of primate well-being?

      Skyner, Lindsay J.; Smith, Tessa E.; University of Chester (Primate Society of Great Britain, 2006-06)
    • Is Wounding Aggression in Zoo-housed Chimpanzees and Ring-tailed Lemurs related to Zoo Visitor Numbers?

      Hosey, Geoff; Melfi, Vicky; Formella, Isabel; Ward, Samantha J.; Tokarski, Marina; Brunger, Dave; Brice, Sara; Hill, Sonya P.; University of Bolton; Taronga Zoo; South Lakes Wild Animal Park; Nottingham Trent University; Chester Zoo; University of Chester (Wiley, 2016-02-29)
      Chimpanzees in laboratory colonies experience more wounds on week days than on weekends, which has been attributed to the increased number of people present during the week; thus the presence of more people was interpreted as stressful. If this were also true for primates in zoos, where high human presence is a regular feature, this would clearly be of concern. Here we examine wounding rates in two primate species (chimpanzees Pan troglodytes and ring-tailed lemurs Lemur catta) at three different zoos, to determine whether they correlate with mean number of visitors to the zoo. Wounding data were obtained from zoo electronic record keeping system (ZIMS™). The pattern of wounds did not correlate with mean gate numbers for those days for either species in any group. We conclude that there is no evidence that high visitor numbers result in increased woundings in these two species when housed in zoos.
    • Isoform-specific Ras signaling is growth factor dependent

      Hood, Fiona E.; Klinger, Bertram; Newlaczyl, Anna U.; Sieber, Anja; Dorel, Mathurin; Oliver, Simon P.; Coulson, Judy M.; Bluthgen, Nils; Prior, Ian A.; University of Liverpool; Universitätsmedizin Berlin; University of Chester (ASCB, 2019-04-11)
      HRAS, NRAS and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform-specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild type or G12V mutated activated Ras isoforms we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling. We find that despite displaying significant Ras activation, the downstream outputs of oncogenic Ras mutants are minimal in the absence of growth factor inputs. The lack of mutant KRAS-induced effector activation observed in SW48 cells appears to be representative of a broad panel of colon cancer cell lines harboring mutant KRAS. For MAP kinase pathway activation in KRAS mutant cells, the requirement for co-incident growth factor stimulation occurs at an early point in the Raf activation cycle. Finally, we find that Ras isoform-specific signaling was highly context dependent and did not conform to the dogma derived from ectopic expression studies.
    • Killer cell Immunoglobulin-like Receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition

      Saunders, Philippa M.; Pymm, Phillip; Pietra, Gabriella; Hughes, Victoria A.; Hitchen, Corinne; O'Connor, Geraldine M.; Loiacono, Fabrizio; Widjaja, Jacqueline M.; Price, David A.; Falco, Michela; et al. (Rockefeller University Press, 2016-04-04)
      NK cells play a key role in immunity, but how HLA-I and KIR3DL1 polymorphism impacts on disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognising the widest array of HLA-I ligands. These differences were further reflected in unctional studies utilising NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005 and *015 polymorphisms are remote from the KIR3DL1-HLA-I interface, the structures of these three KIR3DL1-HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.