Abstract:
:The T cell Ig domain and mucin domain (TIM) proteins form a conserved family of transmembrane cell-surface glycoproteins expressed by a variety of tissues. Each TIM protein contains a single V-type Ig domain, a glycosylated mucin-like domain, a transmembrane domain and a cytoplasmic domain. TIM proteins recognize a diverse array of ligands, including H-ferritin, galectin-9 as well as other TIM family members. In this study, we demonstrate that the Ig domains of murine TIM-1, -3 and -4 display calcium-dependent binding to ligands expressed by murine splenocytes and several non-murine cell lines, indicating non-species-specific ligand recognition. Further, the intrafamilial interaction of various TIM family Ig domains with surface-expressed TIM-1 and TIM-4 requires an intact TIM-1 and TIM-4 glycosylated mucin stalk. Importantly, we also uncovered the previously unrecognized potential for homotypic TIM interactions in forming ligand-receptor pairs. Using a glycan array screen, we identified the novel capacity of the TIM-3 Ig domain to recognize specific carbohydrate moieties, suggesting a role for carbohydrate modification along with protein epitopes in TIM ligand recognition. Identification of the carbohydrate-binding capacity of TIM proteins helps explain the diversity of ligands recognized by this family and adds to our understanding of homotypic and heterotypic interactions between TIM family members.
journal_name
Int Immunoljournal_title
International immunologyauthors
Wilker PR,Sedy JR,Grigura V,Murphy TL,Murphy KMdoi
10.1093/intimm/dxm044subject
Has Abstractpub_date
2007-06-01 00:00:00pages
763-73issue
6eissn
0953-8178issn
1460-2377pii
dxm044journal_volume
19pub_type
杂志文章abstract::To develop a comprehensive catalogue of phenotypic and functional parameters of human CD4(+) T cell differentiation stages, we have performed microarray gene expression profiling on subpopulations of human thymocytes and circulating naive CD4(+) T cells, including CD3(-)CD4(+)CD8(-) intrathymic T progenitor cells, CD3...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh112
更新日期:2004-08-01 00:00:00
abstract::We asked herein whether functional dendritic-like cells could be generated from t(9;22) acute lymphoblastic leukemia (ALL) blasts. We first determined that the combination of interleukin (IL)-1beta, IL-3, IL-7, tumor necrosis factor-alpha, stem cell factor and CD40 ligand was optimal for generating dendritic-like cell...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh139
更新日期:2004-10-01 00:00:00
abstract::We developed a novel approach to probe the molecular basis of TCR recognition of the MHC class I-peptide complex and to determine how constraints placed on peptide binding by the class I molecule influence T cell recognition. We synthesized peptide pairs derived from the N- and C-terminal regions of class I peptide li...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.1.81
更新日期:1997-01-01 00:00:00
abstract::Monoclonal non-specific suppressor factor (MNSF), a lymphokine produced by a murine hybridoma, was originally found to inhibit the generation of lipopolysaccharide (LPS)-induced Ig-secreting cells. Most recently, we demonstrated the recombinant form of the ubiquitin-like segment (rUbi-L) or MNSF beta, an isoform of MN...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.11.1659
更新日期:1996-11-01 00:00:00
abstract::The signaling lymphocytic activation molecule (SLAM) receptor-associated adaptor Ewing's sarcoma-associated transcript-2 (EAT-2) is primarily expressed in innate immune cells including dendritic cells (DCs), macrophages and NK cells. A recent human HIV vaccine study confirmed that EAT-2 expression was associated with ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt061
更新日期:2014-05-01 00:00:00
abstract::T cells of an unique phenotype (CD3+CD4-CD8- alpha beta TCR+) develop in vitro from the hematopoietic progenitors, the majority of which carry homologous alpha beta TCR (V alpha 4J alpha 28/V beta 2D beta 1.1J beta 2.6). In the present study, antigen corresponding to the particular alpha beta TCR was investigated, tak...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.9.1323
更新日期:1994-09-01 00:00:00
abstract::IL-12 has been shown to play a central role in cell-mediated inflammatory reactions through direct activation of T cells and NK cells. IL-12 also strongly influences humoral immunity but these effects have been thought to be indirect and caused by intermediary cytokines. Using flow cytometry, we now show that IL-12 di...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.12.1955
更新日期:1996-12-01 00:00:00
abstract::NK cells limit the emergence of cancers and viral infections by surveillance of 'missing-self' and 'induced-self' ligands, and by direct recognition of pathogen-associated molecules. We examined individual roles for Toll-like receptors (TLRs)-7 and -8 in human NK-cell activation using synthetic, small molecule agonist...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxl046
更新日期:2006-07-01 00:00:00
abstract::Plasmid DNA vectors have been constructed with minigenes encoding a single cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of respiratory syncytial virus (RSV) or from the nucleoprotein of measles virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intrade...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.10.1441
更新日期:1998-10-01 00:00:00
abstract::Whether astrocytes utilize B7:CD28 co-stimulation to activate T cells mediating CNS inflammatory disease is controversial. In this report, primary astrocytes and murine astrocyte lines, generated by immortalization at two different times, day 7 or 45 of culture, were examined for their capability to express B7 co-stim...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.7.1169
更新日期:1999-07-01 00:00:00
abstract::The thymus leukemia antigens (TL) belong to the MHC class Ib family and can be recognized by CD8-dependent or -independent cytotoxic T lymphocytes (CTL) showing TL, but not H-2, restriction. We previously reported that the CTL epitope is TAP independent and in the present study we further characterize the recognition ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg131
更新日期:2003-11-01 00:00:00
abstract::Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). She...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv067
更新日期:2016-04-01 00:00:00
abstract::Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of mutation(s), we p...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt046
更新日期:2014-02-01 00:00:00
abstract::The chicken represents the best-characterized animal model for B cell development in the so-called gut-associated lymphoid tissue (GALT) and the molecular processes leading to B cell receptor diversification in this species are well investigated. However, the mechanisms regulating B cell development and homeostasis in...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxl137
更新日期:2007-02-01 00:00:00
abstract::Recombination activating genes Rag-1 and Rag-2 were isolated on the basis of their ability to confer V(D)J recombination activity when co-expressed in fibroblasts. The mode of action of the confer V(D)J recombination activity when co-expressed in fibroblasts. The mode of action of the products of these genes is not kn...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.2.231
更新日期:1993-02-01 00:00:00
abstract::In vascularized organ transplantation, vascular endothelial cells (EC) confronting recipient T cells are potentially significant APC initiating cellular immune responses that lead to rejection. In the present study, we studied the ability of human EC to stimulate allogeneic T cells and the co-stimulatory molecules inv...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.8.1331
更新日期:1995-08-01 00:00:00
abstract::We report here that different organ grafts are not equally competent to induce tolerance of the host even if they are performed early in development, i.e. before the host's immune system has started to develop. We have grafted the epithelio-mesenchymal rudiment of the bursa of Fabricius between histoincompatible chick...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.6.795
更新日期:1994-06-01 00:00:00
abstract::Spectroscopic methods have been applied to elucidate conformational differences responsible for the immunological diversity of two synthetic multichain copolymers, Tyr1Tyr2Glu3Glu4-poly-DL-Ala--poly-Lys and Tyr1Glu2Tyr3Glu4-poly-DL-Ala--poly-Lys. Despite their far-reaching structural similarity in the epitope peptide ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.6.591
更新日期:1993-06-01 00:00:00
abstract::Myasthenia gravis (MG) is an autoimmune disease, caused by autoantibodies against the muscle acetylcholine receptor (AChR), an oligomeric transmembrane glycoprotein composed of alpha(2)beta gamma delta subunits. The alpha subunit carries in its N-terminal extracellular domain the main immunogenic region (MIR), a group...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.9.1255
更新日期:2000-09-01 00:00:00
abstract::Antibody to phosphatidyl choline (PtC) is produced spontaneously in mice, by approximately 2-10% of naturally occurring CD5+ (B1) B cells in the peritoneum. Much of this antibody is encoded by the VH11 gene associated with a specific V kappa 9 gene. Constraints on the size and structure of the H chain CDR3 have been d...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.11.1365
更新日期:1993-11-01 00:00:00
abstract::The product of the LAG-3 gene is a cell surface protein with significant homology to CD4. It has been suggested that it can serve as a functional equivalent of CD4 and account for the MHC class II-restricted responses which persist in CD4-deficient mice. To test this hypothesis, we have created CD4/LAG-3 double-defici...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.5.725
更新日期:1996-05-01 00:00:00
abstract::Ig are multifunctional molecules with distinct properties assigned to individual domains. To assess the importance of IgM domain assembly in B cell development we generated two transgenic mouse lines with truncated muH chains by homologous integration of the neomycin resistance gene (neo(r)) into exons C(mu)1 and C(mu...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.12.1489
更新日期:2001-12-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg108
更新日期:2003-09-01 00:00:00
abstract::The third complementarity determining regions of heavy chain variable regions (CDRH3) confer the fine specificities of antibodies. The CDRH3 length distribution of all human or all mouse antibodies appears to be more or less random, with the human distribution having a wider spread. Since the Kabat database of aligned...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.12.1801
更新日期:1998-12-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh149
更新日期:2004-10-01 00:00:00
abstract::Dendritic cells (DCs) are specialized antigen-presenting cells that play pivotal roles in initiating immune responses. However, DC maturation is usually strongly restricted by the stromal microenvironment, especially in non-lymphoid tissues, such as skin and mucosa. Although suppression of DC maturation by stromal cel...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn078
更新日期:2008-09-01 00:00:00
abstract::NK cells are functionally controlled by the killer immunoglobulin-like receptor (KIR) family that comprises inhibitory (iKIR) and activating (aKIR) members. Genetic association studies suggest that donors expressing aKIRs next to iKIRs will be superior donors in the setting of hematopoietic stem cell transplantation o...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxx052
更新日期:2017-11-01 00:00:00
abstract::The A6H mAb raised primarily against human renal cell carcinoma (RCC) has previously been shown to bind strongly to RCC, to some degree to colon carcinoma but only marginally to a variety of normal tissues. Immunohistochemical analysis or RCC tissues containing tumor-infiltrating lymphocytes revealed that A6H stained ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.9.1425
更新日期:1995-09-01 00:00:00
abstract::Signal transducer and activator of transcription-1 (STAT1) signaling mediate most biological functions of IFNalpha, IFNbeta and IFNgamma although recent studies indicate that IFNgamma can alter expression of several genes via a STAT1-independent pathway. STAT1 is critical for immunity against a variety of intracellula...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn119
更新日期:2009-01-01 00:00:00
abstract::Earlier studies have suggested that in adults the n-positive allele of the human IgG2 gene is more productive than the n-negative allele. This superiority was seen to be manifested in IgG2 antibody responses to polysaccharides, in the higher serum concentration of total IgG2 in the n/n than in -/- individuals, and in ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/2.4.317
更新日期:1990-01-01 00:00:00