PubMed Health⌕ Search

Biomedical subjects

Louis Du Pasquier

Publications and source records attributed to Louis Du Pasquier.

At least 19 recordsLinked to original sources
PubMed2006

Channel catfish leukocyte immune-type receptors contain a putative MHC class I binding site.

The recent identification of a large and diverse family of leukocyte immune-type receptors (IpLITRs) in channel catfish (Ictalurus punctatus) indicates that immunoglobulin superfamily (IgSF) members related to both mammalian Fc receptors (FcRs) and leukocyte receptor complex (LRC)-encoded proteins exist in fish. In the present study, it was found that IpLITR messages were preferentially up regulated in catfish peripheral blood leukocytes (PBL) and clonal cytotoxic T cells (CTL) after alloantigen stimulation. Detailed sequence analyses of the expressed IpLITR cDNAs from two clonal CTL lines indicated an unexpectedly large array of putative activatory and inhibitory IpLITR-types containing variable numbers of extracellular immunoglobulin (Ig)-like domains. Importantly, all expressed IpLITRs shared similar membrane distal Ig domains (i.e., D1 and D2), suggesting that they may bind a common type of ligand. Sequence alignments and comparative homology modeling revealed that IpLITR domains, D1 and D2, have similar predicted 3-D structural properties with the corresponding domains of the human LRC-encoded leukocyte Ig-like receptor (LILR) family. Furthermore, conservation of key major histocompatibility class I (MHC I)-binding residues were located at similar positions within the membrane distal tip of D1 between representative IpLITRs and group 1 LILRs. Taken together, these results suggest that fish LITRs have an orthologous relationship to LRC-encoded receptors such as the human LILRs and could potentially function as a diverse family of MHC class I-binding receptors.

Amino Acid Sequence↗
PubMed2006

Costimulatory receptors in jawed vertebrates: conserved CD28, odd CTLA4 and multiple BTLAs.

CD28 family of costimulatory receptors is comprised of molecules with a single V-type extracellular Ig domain, a transmembrane and an intracytoplasmic region with signaling motifs. CD28 and cytotoxic T lymphocyte antigen-4 (CTLA4) homologs have been recently identified in rainbow trout. Other sequences similar to mammalian CD28 family members have now been identified using teleost, Xenopus and chicken databases. CD28- and CTLA4 homologs were found in all vertebrate classes whereas inducible costimulatory signal (ICOS) was restricted to tetrapods, and programmed cell death-1 (PD1) was limited to mammals and chicken. Multiple B and T Lymphocyte Attenuator (BTLA) sequences were found in teleosts, but not in Xenopus or in avian genomes. The intron/exon structure of btlas was different from that of cd28 and other members of the family. The Ig domain encoded in all the btla genes has features of the C-type structure, which suggests that BTLA does not belong to the CD28 family. The genomic localization of these genes in vertebrate genomes supports the split between the BTLA and CD28 families.

Amino Acid Motifs↗
PubMed2006

A novel family of diversified immunoregulatory receptors in teleosts is homologous to both mammalian Fc receptors and molecules encoded within the leukocyte receptor complex.

Three novel and closely related leukocyte immune-type receptors (IpLITR) have been identified in channel catfish (Ictalurus punctatus). These receptors belong to a large polymorphic and polygenic subset of the Ig superfamily with members located on at least three independently segregating loci. Like mammalian and avian innate immune regulatory receptors, IpLITRs have both putative inhibitory and stimulatory forms, with multiple types coexpressed in various lymphoid tissues and clonal leukocyte cell lines. IpLITRs have an unusual and novel relationship to mammalian and avian innate immune receptors: the membrane distal Ig domains of an individual IpLITR are related to fragment crystallizable receptors (FcRs) and FcR-like proteins, whereas the membrane proximal Ig domains are related to several leukocyte receptor complex encoded receptors. This unique composition of Ig domains within individual receptors supports the hypothesis that functionally and genomically distinct immune receptor families found in tetrapods may have evolved from such ancestral genes by duplication and recombination events. Furthermore, the discovery of a large heterogeneous family of immunoregulatory receptors in teleosts, reminiscent of amphibian, avian, and mammalian Ig-like receptors, suggests that complex innate immune receptor networks have been conserved during vertebrate evolution.

Amino Acid Sequence↗
PubMed2006

Evidence for a functional second thymus in mice.

The thymus organ supports the development of T cells and is located in the thorax. Here, we report the existence of a second thymus in the mouse neck, which develops after birth and grows to the size of a small lymph node. The cervical thymus had a typical medulla-cortex structure, was found to support T cell development, and could correct T cell deficiency in athymic nude mice upon transplantation. The identification of a regular second thymus in the mouse may provide evolutionary links to thymus organogenesis in other vertebrates and suggests a need to reconsider the effect of thoracic thymectomy on de novo T cell production.

Animals↗
PubMed2006

Survivin increased vascular development during Xenopus ontogenesis.

Survivin is a member of the inhibitor of apoptosis proteins (IAP) family. These proteins contain one to three zinc-binding motifs termed bacculoviral IAP-binding repeats (BIRs). Survivin contains a single BIR motif. Contrary to other members that directly interact with caspases and inhibit apoptosis, Survivin is believed to have both antiapoptotic and proliferative functions. In mammals, Survivin is not detected in most adult tissues except in endothelial cells of newly formed capillaries and large blood vessels. Importantly, Survivin is highly expressed in all common human cancers. To gain a better view of Survivin expression and function during development, we used the amphibian Xenopus developmental model. We show that the genomes of X. laevis, X. tropicalis, Zebrafish, fugu pufferfish, and rainbow trout encode two different Survivin genes (Su1 and Su2), contrary to mammalian genomes, which encode a single one. In X. laevis, these two genes have a differential spatiotemporal transcription pattern. Transgenic expression of Su1 leads to an enlargement of tadpole's blood vessels with an increase in the number of endothelial cells. This effect requires a functional BIR domain and the p34/cdc2 phosphorylation site. It does not seem to rely on the antiapoptotic activity of Su1 as it is not observed in tadpoles overexpressing other antiapoptotic factors such as XIAP or BclXL. We conclude that Su1 ubiquitous gain of function leads directly or indirectly to an increase in blood vessels size via the proliferation of endothelial cells.

Amino Acid Sequence↗
PubMed2005

Germline and somatic diversification of immune recognition elements in Metazoa.

The histories of the immune systems of Metazoa during evolution are envisaged like as many adaptations to the continuous diversification of immune receptors and effectors genes under the pressure of changing environments. A basic diversity of potential immune receptor genes existed in primitive Metazoa. Their subsequent recruitment into immunity, their diversification revolving around the conservation of signaling cascades was paralleled by cell specialization and the introduction of regulatory networks. Polymorphism, duplication and somatic mechanisms of diversification affected independently and still affect different gene families in many phyla, creating a greater variety of immune system exhibiting sometimes little homology but much analogy to one another. Diversity and multiplicity of receptors was generated by duplication and creation of multigene families. Independently in several phyla further diversity is created somatically by alternate splicing, somatic mutation, gene conversion and gene rearrangement. In several instances combinatorial usage of polypeptide chains or genes segments increases the repertoire of the recognition structures. Metazoa had to adapt to the conditions generated by this diversity: the control of expression of multiple genes and the risk of autoimmunity.

Adaptation, Physiological↗
PubMed2005

The chicken leukocyte receptor complex: a highly diverse multigene family encoding at least six structurally distinct receptor types.

The chicken Ig-like receptors (CHIR) have been described as two Ig domain molecules with long cytoplasmic tails containing inhibitory motifs. In this study, we demonstrate that CHIR form a large family, with multiple members showing great sequence variability among members as well as a great diversity in domain organization and properties of the transmembrane and cytoplasmic segments. We characterize various novel receptor types with motifs indicative of inhibitory, activating, or both functions. In addition to the inhibitory receptors with two ITIM, receptors with a single immunoreceptor tyrosine-based switch motif or receptors lacking a cytoplasmic domain were isolated. Activating receptors with a short cytoplasmic domain and a transmembrane arginine assembled with the newly identified chicken FcepsilonRIgamma chain. Three bifunctional receptor types were characterized composed of one or two C2-type Ig-like domains, a transmembrane region with a positively charged residue and combinations of cytoplasmic motifs such as ITIM, immunoreceptor tyrosine-based switch motif, and YXXM. RT-PCR revealed distinct expression patterns of individual CHIR. All receptor types shared a conserved genomic architecture, and in single Ig domain receptors a pseudoexon replaced the second Ig exon. Southern blot analyses with probes specific for the Ig1 domain were indicative of a large multigene family. Of 103 sequences from the Ig1 domain of a single animal, 41 unique sequences were obtained that displayed extensive variability within restricted Ig regions. Fluorescence in situ hybridization localized the CHIR gene cluster to microchromosome 31 and identified this region as orthologous to the human leukocyte receptor complex.

Amino Acid Sequence↗
PubMed2004

An evolutionarily conserved target motif for immunoglobulin class-switch recombination.

Immunoglobulin H class-switch recombination (CSR) occurs between switch regions and requires transcription and activation-induced cytidine deaminase (AID). Transcription through mammalian switch regions, because of their GC-rich composition, generates stable R-loops, which provide single-stranded DNA substrates for AID. However, we show here that the Xenopus laevis switch region S(mu), which is rich in AT and not prone to form R-loops, can functionally replace a mouse switch region to mediate CSR in vivo. X. laevis S(mu)-mediated CSR occurred mostly in a region of AGCT repeats targeted by the AID-replication protein A complex when transcribed in vitro. We propose that AGCT is a primordial CSR motif that targets AID through a non-R-loop mechanism involving an AID-replication protein A complex.

Animals↗
PubMed2004

Endothelial adhesion molecule ESAM binds directly to the multidomain adaptor MAGI-1 and recruits it to cell contacts.

Endothelial cell-selective adhesion molecule (ESAM) is an immunoglobulin-like transmembrane protein associated with endothelial tight junctions (TJ). Based on a yeast two-hybrid screen, we have identified the membrane-associated guanylate kinase protein MAGI-1 as an intracellular binding partner of ESAM. MAGI-1 is a multidomain adaptor protein, which binds to transmembrane, cytoskeletal, and signaling molecules, and has been localized to tight junctions in epithelial cells. MAGI-1 associates with the very C-terminal sequence of ESAM most likely through a PDZ domain-mediated interaction. The direct interaction between ESAM and MAGI-1 was confirmed by pull-down experiments. The two proteins formed stable complexes in transfected Chinese hamster ovary (CHO) cells, which could be immunoisolated. We found MAGI-1 to be associated with cell-cell contacts in human umbilical vein endothelial cells (HUVECs) and in mouse endothelium, where it colocalizes with ESAM. In CHO cells, recruitment of MAGI-1 to cell contacts required the presence of ESAM. Hence, ESAM may be involved in anchoring MAGI-1 at endothelial tight junctions.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Speculations on the origin of the vertebrate immune system.

As one studies more and more the immune systems of invertebrates their multiplicity and diversity increase. On one hand, the number of different local and systemic innate mechanisms (or cascades of mechanisms) increases with every phylum studied, on the other hand the diversity increases within each system as multiple loci and polymorphisms are discovered. Even somatic variation is not restricted to vertebrates. Yet no immune system similar to that of vertebrates characterized by the usage of RAG enzymes, has been found below jawed vertebrates. The availability of genome projects in early chordates allows understanding better the different causal lines that led to the generation of the vertebrate system with its diverse repertoire of antigen receptors generated somatically. This paper singles out a linkage group in human, gathering genes of the Ig superfamily with structural relationships to the antigen receptor JAM/CTX, nectin, or to some haematopoietic cells CD that have homologues in protochordates such as Branchiostoma and Ciona or in more primitive protostomes. The role of virus receptor for many of these clustered genes products provides perhaps one way of envisaging the recruitment of this family in the adaptive immune system from an ancient form of innate antiviral immunity.

Animals↗
PubMed2004

Innate immunity in early chordates and the appearance of adaptive immunity.

In the urochordate Ciona intestinalis some membrane Immunoglobulin superfamily members with ancestral features of antigen receptors are homologs of vertebrate adhesion molecules acting as virus receptors. They include the following: the junction adhesion molecule (reovirus receptor) (JAM), the Cortical thymocyte marker of Xenopus (CTX family) (Coxsackie's virus receptor) and the poliovirus receptor (PVR). In humans these genes belong to the same linkage group, of which 4 paralogous groups exist. This situation is consistent with the notion that the Ciona set of genes would correspond to a preduplication state. In addition, the human region 3q13 and its paralogs, harbour genes remotely related to the nectin family that can be detected in Protostomes (human CRTAM and CD80-86 related to Drosophila Beat). In addition, this linkage group contains several CDs important for the immune system CD166, CD47 and many members of the tetraspanin family. The VC1-like core of the nectin is homologous to the VCI core of the MHC-linked tapasin and to the VC1 segments of, for example, specific antigen receptors of vertebrates, and could be related to a primitive antigen receptor gene. It is suggested that the virus binding property of the members of this family was exploited, and that they were recruited in the vertebrate immune system following the introduction of the somatic rearrangement machinery. In this way the adaptive immune system could have developed from a set of receptors involved in a primitive local innate immunity involving NF-kappaB-mediated apoptosis.

Amino Acid Sequence↗
PubMed2004

On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates.

When and how adaptive immunity emerged is one of the fundamental questions in immunology. Accumulated evidence suggests that the key components of adaptive immunity, rearranging receptor genes and the MHC, are unique to jawed vertebrates. Recent studies in protochordates, in particular, the draft genome sequence of the ascidian Ciona intestinalis, are providing important clues for understanding the origin of antigen receptors and the MHC. We discuss a group of newly identified protochordate genes along with some cold-blooded vertebrate genes, the ancestors of which might have provided key elements of antigen receptors. The organization of the proto-MHCs in protochordates provides convincing evidence that the MHC regions of jawed vertebrates emerged as a result of two rounds of chromosomal duplication.

Animals↗
PubMed2004

Evolution of innate and adaptive immunity: can we draw a line?

Several recent findings in the field of comparative immunology have reinforced the importance of examining the molecular and functional features of immune systems in a variety of organisms. Particularly exciting are the discoveries of a new gene rearrangement mechanism in lampreys and a somatic diversification of mollusk immune genes. These immune features being found in animals previously believed only to have innate immunity, as well as the flood of information on immune genes, molecules and mechanisms in many different creatures, have prompted us to revisit the artificial dichotomy between adaptive and innate immune systems. Although we draw no startling conclusions, we hope to encourage different thought patterns when viewing immune systems.

Adaptation, Physiological↗
PubMed2004

Immunoglobulin superfamily receptors in protochordates: before RAG time.

Urochordates and cephalochordates do not have an adaptive immune system involving the somatic rearrangement of their antigen receptor genes. They do not have antigen-presenting molecules of the major histocompatibility complex (MHC)-linked class I and II types. In the absence of such a system, the status of their genes reflects perhaps a primitive pre-recombination-activating gene (RAG) stage that could suggest the pathway leading to the genesis of the T-cell receptor (TCR) and antibodies. In the genome of Ciona intestinalis, genes that encode molecules with membrane receptor features have been found among many members of the immunoglobulin superfamily (Igsf). They use the domains typical of vertebrate antigen receptors and class I and II: the V, and C1-like domains. These genes belong to two families with recognizable homologs in vertebrates: the junctional adhesion molecule (JAM)/cortical thymocyte marker of Xenopus (CTX) family and the nectin family. The human homologs of these genes segregate in a single unit of four paralogous segments on chromosomes 1q, 3q, 11p, and 21q. These regions contain nowadays several genes involved in the adaptive immune system, and some related members are present in the MHC paralogs as well. They also contain receptor-like genes without homologs in Ciona but with related members in the protostome Drosophila. It looks as if in Ciona one detects what looks like the 'fossil' of one group of genes bound to duplicate and give rise to many crucial elements of the adaptive immune system. The modern homologs of these JAM, CTX, and nectins are all or almost all virus receptors, and the hypothesis is formulated that this property was taken advantage of during evolution to participate in the elaboration of either or both the somatically generated antigen-recognizing receptors and the antigen-presenting molecules.

Animals↗
PubMed2003

Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: "waiting for Godot".

Genome-wide sequence analysis in the invertebrate chordate, Ciona intestinalis, has provided a comprehensive picture of immune-related genes in an organism that occupies a key phylogenetic position in vertebrate evolution. The pivotal genes for adaptive immunity, such as the major histocompatibility complex (MHC) class I and II genes, T-cell receptors, or dimeric immunoglobulin molecules, have not been identified in the Ciona genome. Many genes involved in innate immunity have been identified, including complement components, Toll-like receptors, and the genes involved in intracellular signal transduction of immune responses, and show both expansion and unexpected diversity in comparison with the vertebrates. In addition, a number of genes were identified which predicted integral membrane proteins with extracellular C-type lectin or immunoglobulin domains and intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based activation motifs (ITAMs) (plus their associated signal transduction molecules), suggesting that activating and inhibitory receptors have an MHC-independent function and an early evolutionary origin. A crucial component of vertebrate adaptive immunity is somatic diversification, and the recombination activating genes (RAG) and activation-induced cytidine deaminase (AID) genes responsible for the Generation of diversity are not present in Ciona. However, there are key V regions, the essential feature of an immunoglobulin superfamily VC1-like core, and possible proto-MHC regions scattered throughout the genome waiting for Godot.

Animals↗
PubMed2003

Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co-evolution among MHC class I region genes.

In the frog Xenopus, MHC class I antigen presentation and processing genes (the immunoproteasome LMP2 and LMP7 and the transporter TAP1 and TAP2) seem to be closely linked in a primordial organization. Two distinct lineages of class Ia and LMP7 loci were previously identified, thus strongly suggesting co-evolution among 'class I region' genes. We now show that the Xenopus MHC 'class I region' lies between class II and class III genes and we have isolated two distinct alleles at both the TAP1 and TAP2 loci. The alleles at each locus are remarkably divergent from each other and phylogenetic tree analysis revealed in both cases that they diverged from each other 60-100 million years ago (MYA). For lineage-frequency and linkage analysis, 25 wild-caught X. laevis and 16 X. tropicalis were examined. The two lineages were present in different frequencies for X. laevis and X. tropicalis. Nevertheless, in all cases, the LMP7, TAP1, and TAP2 lineages were found in a set comprising one of the two lineages. Furthermore, like the LMP7 lineages, the TAP lineages were detected in most Xenopus species that diverged from a common ancestor 80-100 MYA, suggesting that the 'class I region' biallelic lineages are under balancing selection.

Alleles↗