Alternative mRNA splicing creates transcripts encoding soluble proteins from most LILR genes.

Leucocyte Ig-like receptors (LILR) are a family of innate immune receptors expressed on myeloid and lymphoid cells that influence adaptive immune responses. We identified a common mechanism of alternative mRNA splicing, which generates transcripts that encode soluble protein isoforms of the majority of human LILR. These alternative splice variants lack transmembrane and cytoplasmic encoding regions, due to the transcription of a cryptic stop codon present in an intron 5' of the transmembrane encoding exon.

Nanogold: a quantitative phase map.

The development of the next generation of nanotechnologies requires precise control of the size, shape, and structure of individual components in a variety of chemical and engineering environments. This includes synthesis, storage, operational environments and, since these products will ultimately be discarded, their interaction with natural ecosystems. Much of the important information that determines these properties is contained within nanoscale phase diagrams, but quantitative phase maps that include surface effects and critical diameter (along with temperature and pressure) remain elusive.

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours.

Developing a prognostic model for traumatic brain injury--a missed opportunity?

Peter Andrews and Neil Young discuss the implications of a study involving the development and validation of new prognostic models for traumatic brain injury.

Stereochemistry of eudesmane cation formation during catalysis by aristolochene synthase from Penicillium roqueforti.

The aristolochene synthase catalysed cyclisation of farnesyl diphosphate (1) has been postulated to proceed through (S)-germacrene A (3). However, the active site acid that reprotonates this neutral intermediate has so far proved difficult to identify and, based on high level ab initio molecular orbital and density functional theory calculations, a proton transfer mechanism has recently been proposed, in which proton transfer from C12 of germacryl cation to the C6,C7-double bond of germacryl cation (2) proceeds either directly or via a tightly bound water molecule. In this work, the stereochemistry of the elimination and protonation reactions was investigated by the analysis of the reaction products from incubation of 1 and of [12,12,12,13,13,13-(2)H(6)]-farnesyl diphosphate (15) with aristolochene synthase from Penicillium roqueforti (PR-AS) in H(2)O and D(2)O.

Neoparamoeba perurans is a cosmopolitan aetiological agent of amoebic gill disease.

Previously we described a new member of the Neoparamoeba genus, N. perurans, and showed that it is an agent of amoebic gill disease (AGD) of Atlantic salmon Salmo salar cultured in southeast Tasmania, Australia. Given the broad distribution of cases of AGD, we were interested in extending our studies to epizootics in farmed fish from other sites around the world.

The inhibitory receptor LILRB1 modulates the differentiation and regulatory potential of human dendritic cells.

Dendritic cells (DCs) link innate and adaptive immunity, initiating and regulating effector cell responses. They ubiquitously express members of the LILR (ILT, LIR, CD85) family of molecules, some of which recognize self-HLA molecules, but little is known of their possible functions in DC biology. We demonstrate that the inhibitory receptor LILRB1 (ILT2, LIR1, CD85j) is selectively up-regulated during DC differentiation from monocyte precursors in culture.

Synthetic efficiency in enzyme mechanisms involving carbocations: aristolochene synthase.

An intramolecular proton-transfer mechanism has been proposed for the carbocationic cyclization of farnesyl pyrophosphate (FPP) to (+)-aristolochene catalyzed by aristolochene synthase. This novel mechanism, which is based on results obtained by high-level ab initio molecular orbital and density functional theory calculations, differs from the previous proposal in the key step of carbocation propagation prior to the formation of the bicyclic carbon skeleton. Previously, germacrene A was proposed to be generated as an intermediate by deprotonation of germacryl cation followed by reprotonation of the C6-C7 double bond to yield eudesmane cation.

Competitive inhibition of aristolochene synthase by phenyl-substituted farnesyl diphosphates: evidence of active site plasticity.

Analogues of farnesyl diphosphate (FPP, ) containing phenyl substituents in place of methyl groups have been prepared in syntheses that feature use of a Suzuki-Miyaura reaction as a key step. These analogues were found not to act as substrates of the sesquiterpene cyclase aristolochene synthase from Penicillium roqueforti (AS). However, they were potent competitive inhibitors of AS with K(I)-values ranging from 0.

Nature of allelic sequence polymorphism at the KIR3DL3 locus.

KIR3DL3 is a framework gene of the Leukocyte Receptor Complex, present in all individuals and haplotypes analysed to date. We describe 17 novel KIR3DL3 alleles, including seven single nucleotide polymorphic (SNP) positions within the coding region. Sequence variation within introns included a VNTR within intron 1.

Does memory improve with age? CD85j (ILT-2/LIR-1) expression on CD8 T cells correlates with 'memory inflation' in human cytomegalovirus infection.

CMV-specific memory CD8(+) T cells accumulate over time to reach high frequencies amongst peripheral blood lymphocytes - a phenomenon termed 'memory inflation'. Using tetramer staining on samples from a large number of subjects and multivariate regression analysis, we were able to relate this to the phenotype of CD8(+) T cells. We made the following observations: (i) CD85j (ILT-2/LIR-1) was highly expressed alongside CD57 - an established effector memory marker - on CMV-specific CD8(+) T cells; (ii) on CD8(+) T cells as a whole, with increasing age, CD57 and CD85j (ILT-2/LIR-1) expression increased whereas CCR7 expression decreased, indicating increasing maturation of the total CD8(+) T-cell compartment with age; (iii) unit increases in the percentage of CMV-specific CD8(+) T cells expressing CD57 and CD85j (ILT-2/LIR-1) were associated with incremental expansion of these T-cell populations; (iv) CMV seropositivity is associated with a marked effect on the overall phenotype of CD8(+) T cells (at any given age, CMV seropositivity is associated with an 18.

Immunobiology of natural killer lymphocytes in transplantation.

Natural killer (NK) lymphocytes are powerful effector cells of the peripheral immune system. NK cell functions are controlled by the expression of a variety of cell surface receptors with either inhibitory or activating roles. The genetic and functional diversity of this repertoire of receptors and the role of human leukocyte antigen class I histocompatibility molecules as a major group of NK receptor ligands endows NK cells with an innate alloreactive capacity.

Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D.

We characterized two novel members of the RAET1/ULBP gene cluster, RAET1E and RAET1G. The encoded proteins were similar to the ULBP in their class I-like alpha1 and alpha2 domains, but differed in that, instead of being GPI-anchored, their sequences were type 1 membrane-spanning molecules. Both proteins were capable of being expressed at the cell surface.

Frequency and phenotype of circulating Valpha24/Vbeta11 double-positive natural killer T cells during hepatitis C virus infection.

Natural killer T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, Valpha24/Vbeta11 double positive, in hepatitis C virus (HCV) infection. Lower frequencies of this population were detected in the blood of HCV PCR-positive patients than in controls.

Genetic control of human NK cell repertoire.

Through differential killer cell Ig-like receptor (KIR) and CD94:NKG2 gene expression, human NK cells generate diverse repertoires, each cell having an inhibitory receptor for autologous HLA class I. Using a new method for measuring repertoire difference that integrates multiple flow cytometry parameters, we found individual repertoire stability, but population variability. Correlating repertoire differences with KIR and HLA genotype for 85 sibling pairs reveals the dominant influence of KIR genotype; HLA genotype having a subtle, modulating effect on relative KIR expression frequencies.

KIR expression shapes cytotoxic repertoires: a developmental program of survival.

We hypothesize a sequential program of expression of the leukocyte-receptor complex (LRC) in CD8+T cells, associated with cellular activation and the subsequent establishment of immune homeostasis through resistance to apoptosis. This program, which is consistent with the linear development of memory CD8+ T cells, represents an ordered expression of genes during differentiation, analogous to expression of the homeobox- or globin-gene clusters. Our model not only has implications for the development and maintenance of T-cell memory but also, relates to the formation of LRC repertoires in other cell types, particularly, the development of killer-cell Ig-like receptor (KIR) repertoires in natural-killer-cell precursors.