Abstract:
:Susceptibility and resistance to type 1 diabetes are associated with MHC class II alleles that carry non-Asp and Asp at residue 57 of their beta chain respectively. The effect of Asp or non-Aspbeta57 may relate to a differential ability of distinct class II molecules to bind specific immuno-pathogenic peptides. Recent studies in man and mouse have revealed that some type 1 diabetes-predisposing non-Aspbeta57 class II molecules (i.e. DQ8, DR4Dw15 and I-Ag7) preferentially bind peptides with a negatively charged anchor residue at P9. It has been suggested that this is a common feature of type 1 diabetes-predisposing class II molecules. The molecular explanation for such a phenomenon could be that class II beta chains with Aspbeta57 form a salt bridge between Aspbeta57 and a conserved Arg of the a chain, whereas in non-Aspbeta57 molecules the Arg is unopposed and free to interact with negatively charged P9 peptide anchor residues. We have investigated the specificity of the P9 pocket of the type 1 diabetes-associated DQ2 molecule and in particular examined for charge effects at this anchor position. Different approaches were undertaken. We analyzed binding of a high-affinity binding ligand and P9-substituted variants of this peptide, and we analyzed the binding of a set of synthetic random peptide libraries. The binding analyses were performed with wild-type DQ2 and a mutated DQ2 with Ala at beta57 substituted with Asp. Our results indicate that the wild-type DQ2 (non-Aspbeta57) prefers large hydrophobic residues at P9 and that there is no particular preference for binding peptides with negatively charged residues at this position. The specificity of the P9 pocket in the mutated DQ molecule is altered, indicating that the beta57 residue contributes to determining the specificity of the P9 pocket. Our data do not lend support to the hypothesis that all non-Asp beta57 class II molecules predispose to development of disease by binding peptides with negatively charged P9 anchor residues.
journal_name
Int Immunoljournal_title
International immunologyauthors
Quarsten H,Paulsen G,Johansen BH,Thorpe CJ,Holm A,Buus S,Sollid LMdoi
10.1093/intimm/10.8.1229subject
Has Abstractpub_date
1998-08-01 00:00:00pages
1229-36issue
8eissn
0953-8178issn
1460-2377journal_volume
10pub_type
杂志文章abstract::Programmed cell death-1 (PD-1, Pdcd1), an immunoreceptor belonging to the CD28/CTLA-4 family negatively regulates antigen receptor signaling by recruiting protein tyrosine phosphatase, SHP-2 upon interacting with either of two ligands, PD-L1 or PD-L2. Because of the wide range of ligand distribution in the body, its b...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxm057
更新日期:2007-07-01 00:00:00
abstract::The regulation of MHC class II expression by the class II transactivator (CIITA) is complex and differs in various cell types depending on the relative activity of three CIITA promoters. Here we show that, in plasma cell tumors, the deacetylase inhibitor trichostatin A (TSA) elicits PIII-CIITA but does not activate th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh326
更新日期:2005-11-01 00:00:00
abstract::NK cells were first identified in 1975 and represent the prototypical group 1 innate lymphoid cell (ILC). More recently, the discovery of new members of the ILC family has highlighted the complexity of this innate lymphoid lineage. Importantly, it has been recognized that different subsets exist within the group 1 ILC...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxv051
更新日期:2016-01-01 00:00:00
abstract::Peyer's patch (PP) organogenesis proceeds through three histologically distinct steps: formation of organizing centers expressing VCAM-1 and ICAM-1 in segregated regions of the intestine at 15.5 days post-coitus (d.p.c.) (step I), accumulation of blood cells expressing different sets of surface markers to this region ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.5.643
更新日期:1999-05-01 00:00:00
abstract::IL-7 is a required factor for T-cell homeostasis. Because of low expression levels and poor reagent availability, the cellular sources of IL-7 have proven challenging to characterize. In this study, we describe a reporter mouse in which enhanced GFP is expressed from the endogenous Il7 locus. We show that IL-7 is prod...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt012
更新日期:2013-08-01 00:00:00
abstract::At least three B cell subsets, B-1a, B-1b and B-2, or conventional B cells are present in the mouse periphery. Here we demonstrate that B-1 cells spontaneously proliferate in stationary cultures of normal adherent mouse peritoneal cells. B-1 cells were characterized by morphology, immunohistochemistry and flow cytomet...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.9.1193
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, and one of these, IL-1β, has been previously implicated in inflammatory skin disease. T(h)17 cells, a subset of T(h) cells involved in autoimmunity and inflammation, possess IL-1β receptors and secrete cytokin...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxr110
更新日期:2012-03-01 00:00:00
abstract::Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunizat...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.8.1139
更新日期:1998-08-01 00:00:00
abstract::MicroRNAs 125a and 125b are predicted to be able to bind to the B lymphocyte-induced maturation protein-1 (BLIMP-1) and IFN regulatory protein-4 (IRF-4) transcription factors, which are essential for plasma cell differentiation. A computational survey of the human and mouse genomes revealed that miR-125a and miR-125b ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq042
更新日期:2010-07-01 00:00:00
abstract::In this study, we analyzed peripheral blood CD4+CD8+ double-positive (DP) lymphocytes in adult cynomolgus monkeys (Macaca fascicularis). Forty of 55 monkeys had > 5% of the peripheral blood DP subpopulation (9.3 +/- 5.9%; mean +/- SD) in peripheral blood lymphocytes (PBL) in contrast to a low percentage of peripheral ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.4.591
更新日期:1997-04-01 00:00:00
abstract::House dust mite (HDM) is a common allergen of allergic asthma. Eosinophils are principal effector cells of allergic inflammation and their adhesion onto human bronchial epithelial cells is mediated by a CD18-intracellular adhesion molecule-1 (ICAM-1)-dependent interaction. We studied the effects of HDM Dermatophagoide...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxl065
更新日期:2006-08-01 00:00:00
abstract::To study the paracrine effect of IL-10 on autoimmune insulitis and diabetes, we produced IL-10 transgenic non-obese diabetic (NOD) mice (NOD-IL-10) in which murine IL-10 was expressed in pancreatic islet A cells under the control of a rat glucagon promoter without directly manipulating pancreatic islet B cells. Among ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.12.1927
更新日期:1994-12-01 00:00:00
abstract::We have isolated two cDNA clones encoding the guinea pig receptor for the Fc portion of IgG2 (Fc gamma 2R) from a guinea pig peritoneal macrophage cDNA library. Analysis of the predicted amino acid sequence of the one cDNA clone indicated that the guinea pig Fc gamma 2R is a type I transmembrane protein and has approx...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.9.1335
更新日期:1996-09-01 00:00:00
abstract::Natural killer (NK) cells are a major FcγRIIIA-expressing lymphocyte population that mediate antibody-dependent cellular cytotoxicity. Although NK cells are critical for immunity against viruses and tumors, they are also activated in the joints of patients with rheumatoid arthritis (RA) and may be involved in disease ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxz010
更新日期:2019-04-26 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::CD45 is a receptor tyrosine phosphatase essential for TCR signaling. One isoform, CD45RB, is down-regulated in memory cells and targeting CD45RB with a specific antibody has been shown to inhibit graft rejection. Its role in immunity to infection, however, has not been tested. Here, we report the effect of anti-CD45RB...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh367
更新日期:2006-02-01 00:00:00
abstract::Recent studies have shown that tumor cells acquire escape mechanisms to evade host immunity in the tumor microenvironment. Two key immune checkpoint pathways mediated by immunosuppressive co-signaling, the first via programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-1/PD-L1) and the second via CTLA-4 and B7 (CTLA-4/...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxw020
更新日期:2016-07-01 00:00:00
abstract::In vaccine development, a major objective is to induce strong, specific T cell responses. This might be obtained by targeting antigen to cell surface molecules that efficiently channel the antigen into endocytic compartments for loading of MHC molecules. Antibodies have been used to deliver antigen; however, it is imp...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxf110
更新日期:2002-12-01 00:00:00
abstract::BALB.xid mice, carrying an X-linked mutation leading to the absence of CD5+ B cells, are highly resistant to Trypanosoma cruzi infection. These mice clear blood parasites in the acute phase of infection and do not develop the inflammatory infiltration characteristically observed in the chronic phase of susceptible str...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.8.1213
更新日期:1996-08-01 00:00:00
abstract::The contribution of the HLA-DRB1, -B3, and -B5 gene products in the recognition of Dermatophagoides spp. (house dust mite) by helper T cells isolated from an atopic individual (HLA-DRw12, DR7; DRw52b) with perennial rhinitis was investigated. Using a panel of histocompatible and histoincompatible accessory cells, the ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/2.9.885
更新日期:1990-01-01 00:00:00
abstract::The class II transactivator (CIITA) controls both the constitutive and IFN-gamma inducible expression of HLA-D genes. In addition, through the squelching of another transactivator CREB-binding protein, CIITA was more recently shown to have a wider cellular function, including cell cycle control or cellular response to...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxf060
更新日期:2002-08-01 00:00:00
abstract::Non-obese diabetic mice spontaneously develop a type 1 diabetes. The entry of leukocytes in the islets of Langerhans was studied in untreated and in irradiated mice. FITC-labeled cells from spleen, lymph nodes or bone marrow of healthy or diabetic donors did home to the inflamed islets of unmanipulated recipients. B a...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.12.1905
更新日期:1995-12-01 00:00:00
abstract::Trypanosoma cruzi, the agent of Chagas disease contains a major cysteine proteinase, cruzipain (Cz), with an unusual carboxyl-terminal extension (C-T). We have previously reported the presence of sulfate groups in the N-linked oligosaccharide chains of this domain. In order to evaluate the immune responses to sulfated...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm149
更新日期:2008-04-01 00:00:00
abstract::Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity. In the present study, we investigated the in vivo involvement of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) using Tyk2-deficient mice. Hind paws of wild-type mice showed massive s...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxr057
更新日期:2011-09-01 00:00:00
abstract::The two-signal model states that activation of naive T cells requires a signal 1 stimulus through the TCR and a co-stimulatory signal 2. By contrast, signal 1 alone is sufficient for pre-activated T cells. Recently, however, it has been shown that under certain conditions T cells can bypass the requirement for co-stim...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.5.619
更新日期:1998-05-01 00:00:00
abstract::Murine bone marrow-derived macrophages (BMM) are able to inhibit the intracellular growth of Mycobacterium bovis and Mycobacterium tuberculosis H37Rv after activation with recombinant (r) IFN and growth inhibition is mediated by reactive nitrogen intermediates (RNI) derived from L-arginine. We now demonstrate that tum...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.5.693
更新日期:1994-05-01 00:00:00
abstract::NOD mice spontaneously develop type I diabetes resulting from autoimmune destruction of their insulin-producing beta cells. Among the self-antigens targeted by NOD autoimmune T cells is a peptide, p277, from the sequence of the 60 kDa heat shock protein (hsp60). Common to the anti-p277 T cell populations of NOD mice i...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.6.957
更新日期:1999-06-01 00:00:00
abstract::Analysis of immunoglobulin expression in mice transgenic for either a kappa light chain (driven by the kappa enhancer) or lambda light chain (driven by the IgH enhancer) revealed that the transgenic light chains are expressed by the majority of B lymphocytes in the neonatal mice. However, the proportion of B cells tha...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/1.5.509
更新日期:1989-01-01 00:00:00
abstract::It has been demonstrated that in vivo T cell priming requires CD154-CD40 interaction, which is suggested to be critical in the induction of co-stimulatory activities on antigen-presenting cells (APC). In the current study, we demonstrate that in vivo administration of a high dose of a superantigen, staphylococcal ente...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg080
更新日期:2003-07-01 00:00:00
abstract::Deletion of alpha i2 subunit of heterotrimeric G proteins induces a 2-4-fold increase in the proportions of CD4 and CD8 single-positive (SP) thymocytes as compared with wild-type littermates, but how G alpha i2 is involved in thymocyte development is unknown. To determine a role for G alpha i2 in a specific developmen...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh204
更新日期:2005-03-01 00:00:00