bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cathepsin B cleavage of Ii from class II MHC alpha- and beta-chains.
Authors: Reyes V E , Lu S , Humphreys R E 
Published: December 2022

Abstract
Class II MHC-associated invariant chain (Ii) might regulate binding of digested peptides to the Ag binding site (desetope) of class II MHC proteins by directly or allosterically blocking that site until cleavage and release of Ii from MHC alpha- and beta-chains at the time of peptide charging. We examined the cleavage and release of Ii from class II MHC alpha/beta Ii trimers by cathepsin B, which has been shown by others to colocalize with class II MHC molecules in intracellular compartments and to generate antigenic peptide fragments. Cathepsin B at pH 5.0 cleaved and released Ii from class II MHC alpha- and beta-chains. Cathepsin B digested Ii from alpha- and beta-chains in a dose-dependent fashion, yielding 23-, 21-, and 10-kDa fragments. Blockage of cathepsin B activity with leupeptin restored the 2D(nonequilibrium pH gradient gel electrophoresis/SDS) PAGE patterns of Ii and sialic acid-derivatized forms of Ii seen without the protease. The fragmentation pattern of cathepsin D treatment was different from that of cathepsin B, yielding 25-kDa intermediates.
Regulation of phospholipase D-induced hydrolysis of choline-containing phosphoglycerides by cyclic AMP in human neutrophils.
Authors: Agwu D E , McCall C E , McPhail L C 
Published: December 2022

Abstract
In human neutrophils, the chemotactic tripeptide FMLP and the protein kinase C activator PMA stimulate the breakdown of 1-O-[3H]alkyl-2-acyl-sn-glycero-3-phosphocholine ([3H]EAPC) and the formation of 1-O-[3H]alkyl-2-acyl-phosphatidic acid ([3H]-EAPA) and 1-O-[3H]alkyl-2-acylglycerol ([3H]EAG) via mechanism(s) that may involve the activation of phospholipase D. We have investigated the regulation of phospholipase D by determining the effects of elevation of intracellular levels of cAMP on receptor-mediated and PMA-induced breakdown of [3H]-EAPC and formation of products. Pretreatment of neutrophils with either 10(-3) M dibutyryl-cAMP or 10(-5) M PGE2, in the presence of 4 x 10(-4) M isobutylmethylxanthine (IBMX), inhibited FMLP- and leukotriene B4-induced breakdown of [3H]EAPC and formation of [3H]EAPA and [3H]EAG. Inhibition was apparent at all time points of stimulation examined (15-120 s). In addition, the mass of diradyl-phosphatidic acid was decreased in FMLP-stimulated neutrophils pretreated with PGE2 and IBMX. In contrast, pretreatment of cells with PGE2 and IBMX did not inhibit PMA-induced breakdown of [3H]EAPC and the formation of products at 3 and 10 min after stimulation. Furthermore, formation of 1-O-[3H]alkyl-2-acyl-phosphatidylethanol, produced by phospholipase D in the presence of ethanol by a transphosphatidylation reaction, was significantly inhibited by pretreatment of cells with PGE2 and IBMX in FMLP- but not PMA-stimulated neutrophils. This differential modulation by cAMP of receptor-mediated and PMA-induced activation of phospholipase D suggests agonist-dependent activation of separate pathways and/or activation of separate phospholipase D enzymes. Thus, cAMP elevation may exert inhibitory effects directly on the phospholipase D activated by FMLP and/or on sites proximal to the enzyme that are involved in signal transmission.
Initiation of delayed-type hypersensitivity by low doses of monoclonal IgE antibody. Mediation by serotonin and inhibition by histamine.
Authors: Ptak W , Geba G P , Askenase P W 
Published: December 2022

Abstract
Elicitation of delayed-type hypersensitivity (DTH) responses by DTH effector T cells requires a prior phase of DTH initiation. This consists of an immediate hypersensitivity-like response mediated by Ag-specific DTH-initiating factors that are analogous to IgE antibodies in that they sensitize tissue mast cells for release of the vasoactive amine serotonin (5-HT). Experiments were conducted to determine whether IgE mAb injected i.v., or 5-HT injected locally, could initiate DTH. It was found that small doses of IgE (1 microgram/mouse), or of 5-HT (50 to 500 ng locally), which mediated small immediate responses, were optimal for DTH initiation. Even lower doses of IgE (10 ng/mouse), or of 5-HT (5 ng locally), which did not mediate macroscopically measurable immediate responses, were capable of DTH initiation. Higher doses of IgE (10 to 100 micrograms/mouse), which mediated large immediate responses, were not able to initiate DTH. A similar dose response for DTH initiation was found with IgG1 mAb, which is another mast cell-sensitizing isotype of Ig. The inability of high doses of IgE or IgG1 to mediate DTH initiation was probably caused by local release of large inhibitory amounts of histamine, because systemic treatment with the histamine-2 receptor antagonist cimetidine allowed high doses of IgE to initiate DTH. Thus, IgE and IgG1 antibodies could initiate DTH via release of small amounts of 5-HT, but simultaneous release of large amounts of histamine were inhibitory, probably via an effect on histamine-2 receptors of recruited T cells. We concluded the following: 1) IgE or IgG1 antibodies can initiate DTH; 2) DTH initiation need not be associated with macroscopically detectable early responses; 3) mast cell release of 5-HT acts positively whereas release of histamine acts negatively in murine DTH; 4) Ag-specific factors are not the only mechanism of DTH initiation.
Junctional diversity of H and L chains allows the coexpression of two mutually exclusive idiotopes (IdI104 and IdI558).
Authors: Rueff-Juy D , Marche P N , Drapier A M , Cazenave P A 
Published: December 2022

Abstract
The molecular basis for the unexpected coexpression of the individual Id (IdI)558 and IdI104 Id by anti-alpha(1-3) DEX antibody (Ab) (126.33 and 414.2) derived from the MPW wild mouse strain has been investigated by the comparison of the structures of their VH and V lambda 1 chain regions with those of two other MPW-derived Ab (262.9 and 16.3) expressing either IdI558 or IdI104 Id. Our data show that 262.9 and 16.3 Ab display identical V lambda 1 and very similar VH regions when compared with BALB/c anti-alpha (1-3) dextran Ab expressing IdI104 or IdI558, respectively. The two Ab (414.2 and 126.33) that express both IdI104 and IdI558 Id display two main features. First, their VH CDR3 are different from those found in IdI104 or IdI558 expressing anti-alpha(1-3) dextran Ab. Second, their V lambda 1 are identical to those from BALB/c origin except for the presence of an additional residue, a phenylalanine at position 95A of CDR3. This additional residue is encoded by the V lambda 1 gene segment and results from a hitherto undescribed V lambda 1-J lambda 1 junction. The alteration of the length of the V lambda 1 CDR3 loop, in conjunction with particular residues within VH CDR3, allows the coexpression of two Id that were found to be mutually exclusive in laboratory mice.
A subset of asialo GM1+ cells play a protective role in the occurrence of graft-versus-host disease in mice.
Authors: De Ruysscher D , Sobis H , Vandeputte M , Waer M 
Published: December 2022

Abstract
In three different murine models of bone marrow (BM) transplantation the capacity of asialo GM1+ cells to suppress graft-vs-host disease (GVHD) was investigated. In a first model, total lymphoid irradiation (TLI)-treated BALB/C mice were given 1 mg of anti-asialo GM1 antibody. This led to the disappearance of functional suppressor cells after TLI. Injections of anti-asialo GM1 into TLI-treated BALB/C mice before infusion of 30 x 10(6) fully allogeneic (C3H) BM cells, led to a significantly decreased survival rate as compared to TLI-treated mice injected with control serum before BM transplantation (survival 29 and 83%, respectively, at 120 days after transplantation, p = 0.0032 log rank). The mortality of the former group was due to GVHD as 1 degree all dying animals showed clinical and histologic signs of GVHD, 2 degrees all animals were chimeric and 3 degrees mice receiving no or syngeneic BALB/C BM had excellent survival rates excluding BM aplasia or increased susceptibility for infections as reason for the mortality of the allogeneic BM recipients. In a second model, asialo GM1+ cells were removed in vitro from the C3H BM inoculum before injection into lethally irradiated (9 Gy) BALB/C recipients. In mice kept in specific pathogen-free conditions, this procedure resulted into a significant mortality (12/12) as compared to mice receiving BM pretreated with control serum (1/12, p = 0.0001 log rank). When kept in conventional housing, GVHD occurred in both groups but much earlier in the group receiving anti-asialo GM1-treated BM (median survival time 6 vs 46 days for the control mice, p = 0.001 log rank). No animal receiving anti-asialo GM1 and treated with syngeneic BM died, thus excluding toxicity, increased susceptibility to infections, or decreased graft take as a cause of mortality. In a last model, asialo GM1 cells were removed from syngeneic BM in a BM transplantation model in which T cell-depleted syngeneic (BALB/C) and non-T cell-depleted allogeneic (C3H) BM was administered to lethally irradiated (9 Gy) BALB/C mice. Also in this model GVHD-related mortality only occurred in the group of mice receiving syngeneic BM from which asialo GM+ cells were depleted before infusion (3/12). Our experiments thus clearly show that asialo GM1+ cells from both recipient (the TLI model) as well as donor origin (the TBI experiments) can suppress the occurrence of GVHD.
Colchicine is a potent adjuvant for eliciting T cell responses.
Authors: Titus R G 
Published: December 2022

Abstract
The cytotoxic drug colchicine when administered to mice in conjunction with Ag was shown to have a strong adjuvant effect in generating a specific plaque-forming cell response to the protein Ag OVA, human gamma-globulin and BSA. Dissection of this phenomenon revealed that several T cell activities, including Th function, Ag-induced T cell proliferation and T cell-mediated delayed-type hypersensitivity, were also specifically induced by treating mice with colchicine + Ag. The adjuvant effect of colchicine was observed when the drug and Ag were injected in soluble form, i.e., no vehicle (e.g., oil, liposome) was necessary. The potency of colchicine as an adjuvant was equal to or more than that of conventional adjuvants such as CFA or alum.
Cytokine secretion by C3H-lpr and -gld T cells. Hypersecretion of IFN-gamma and tumor necrosis factor-alpha by stimulated CD4+ T cells.
Authors: Davidson W F , Calkins C , Hügins A , Giese T , Holmes K L 
Published: December 2022

Abstract
Mice homozygous for lpr and gld develop profound lymphadenopathy characterized by the expansion of two unusual T cell subsets, a predominant Ly-5(B220)+ CD4- CD8- double negative (DN) population and a minor CD4 dull+ Ly-5(B220)+ population. The mechanisms promoting lymphoproliferation are unknown, but one possibility is a abnormality in the production of cytokines that regulate T cell growth. In the present report, unfractionated LN cells and sorted T cell subsets from C3H-lpr, -gld, and -+/+ mice were compared for spontaneous and induced secretion of a spectrum of lymphokines. In addition, CD4+, CD4 dull+ Ly-5(B220)+, and DN T cells were examined for expression of CD3 epsilon, TCR-alpha/beta heterodimers, Ly-6C, and CD44 and for proliferative responses to immobilized anti-TCR mAb and cofactors. These studies revealed that sorted DN T cells did not secrete IL-3, IL-4, IL-5, IL-6, GM-CSF, TNF-alpha, or IFN-gamma spontaneously or after TCR-alpha/beta cross-linking. In contrast, stimulated unfractionated lpr and gld LN cells proliferated strongly and secreted high levels of IFN-gamma and TNF-alpha and low levels of IL-3, IL-4, and IL-6. Despite a 5- to 10-fold deficit in the frequency of CD4+ and CD8+ T cells, cytokine secretion by lpr and gld LN generally exceeded that of +/+ LN. Comparisons of cytokine secretion by stimulated CD4+ T cells revealed that +/+, lpr, and gld CD4+ Ly-5(B220)- T cells proliferated strongly, but only lpr and gld cells produced significant levels of IFN-gamma. The lpr and gld CD4+ T cells also produced higher levels of TNF-alpha and IL-2 than +/+ cells. In contrast to normal CD4+ T cells, lpr and gld CD4+ Ly-5(B220)+ T cells proliferated weakly and did not secrete TNF-alpha, IL-2, or, in most experiments, IFN-gamma after stimulation. Phenotypic studies of T cell subsets revealed that unstimulated lpr and gld CD4+ Ly-5(B220)- T cells express significantly higher levels of CD44 than +/+ CD4+ T cells. In addition, CD4 dull+ Ly-5(B220)+ cells closely resembled DN T cells in size and expression of TCR-alpha/beta, CD3epsilon, CD44, and Ly-6C. Since elevated CD44 expression is generally associated with T cell activation and only previously activated normal CD4+ T cells produce high levels of IFN-gamma in vitro, our data suggest that lpr and gld CD4+ Ly-5(B220)- T cells contain a higher than normal proportion of primed or memory T cells and thus may be polyclonally activated in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)
Role of CD11/CD18 in adhesion and transendothelial migration of T cells. Analysis utilizing CD18-deficient T cell clones.
Authors: Kavanaugh A F , Lightfoot E , Lipsky P E , Oppenheimer-Marks N 
Published: December 2022

Abstract
The role of leukocyte function-associated Ag-1 (LFA-1) (CD11a/CD18) in T cell-endothelial cell (EC) interactions was assessed by utilizing CD11a/CD18-deficient T cell clones generated from a patient with leukocyte adhesion deficiency (LAD). The ability of these clones to bind to and migrate through monolayers of EC in vitro was compared with that of clones generated in a similar manner from normal controls. The LAD clones bound to EC to a similar extent as the controls. The contribution of other cell surface adhesion molecules was assessed with mAb blocking experiments. It was found that part of the EC binding by these CD11a/CD18-deficient clones was mediated by an interaction of very late Ag-4 (VLA-4) with vascular cell adhesion molecule-1 (VCAM-1) on the EC. In contrast to their normal ability to bind to EC, the capacity of the LAD clones to migrate through EC monolayers was significantly less than that of the control clones. This impairment in migration was not related to decreased intrinsic motility. Moreover, neither phorbol ester stimulation of the LAD clones nor IL-1 stimulation of the EC increased the capacity of the clones to migrate through EC monolayers, although binding to EC was augmented by both treatments. Only a minimal percentage of the migration of either control or LAD clones was inhibited by mAb to VLA-4 or VCAM-1. These data demonstrate that LFA-1 plays a central role in the transendothelial migration of T cells. In the absence of LFA-1, T cells retain the ability to bind to EC because of the activity of other receptor/ligand pairs, including VLA-4/VCAM-1. Finally, it is likely that, during both binding and transendothelial migration of T cells, additional cell surface molecules play a role.
IL-4 inhibits IL-2 synthesis and IL-2-induced up-regulation of IL-2R alpha but not IL-2R beta chain in CD4+ human T cells.
Authors: Gayá A , de la Calle O , Yagüe J , Alsinet E , Fernández M D , Romero M , Fabregat V , Martorell J , Vives J 
Published: December 2022

Abstract
There is growing evidence to suggest a regulatory role of IL-4 in the immune system affecting both proliferation and lymphokine production. In the present work we have analyzed the effect of IL-4 on IL-2 and IFN-gamma synthesis by stimulating CD4+ human T cells (+10% accessory cells) with Con A in the presence of several doses (1 to 100 U/ml) of human rIL-4. The results showed an impaired IL-2 and IFN-gamma synthesis in the presence of IL-4. This inhibition was dose dependent and was evident only when IL-4 was added in the first 2 h of culture. Moreover, the external addition of IL-2 did not revert the inhibitory effect of IL-4 on IL-2 and IFN-gamma synthesis induced by Con A. We have also analyzed the effect of IL-4 on the expression of both alpha- and beta-chains of the IL-2R. Although the expression of IL-2R alpha mRNA was not modified after 6 h in culture in the presence of IL-4, a decrease was observed at 24 and 48 h. The addition of rIL-2 showed that the inhibition in IL-2R alpha expression could be explained by an impairment in the up-regulatory signal transmitted through the IL-2R. In addition to this, IL-4 did not modify the IL-2R beta mRNA expression at 6 and 24 h although a decreased expression was observed at 48 h which could be explained by the defective IL-2 production. The differential effect of IL-4 on the up-regulatory effect of IL-2 in the expression of IL-2R alpha and IL-2R beta suggest the existence of different regulatory mechanisms acting on the expression of both chains.
Mouse IL-1 receptor antagonist protein. Molecular characterization, gene mapping, and expression of mRNA in vitro and in vivo.
Authors: Zahedi K , Seldin M F , Rits M , Ezekowitz R A , Whitehead A S 
Published: December 2022

Abstract
The IL-1R antagonist protein (IL-1RN/IL-1rn) is a member of the IL-1 family of inflammatory mediators. We have isolated and analyzed a mouse IL-1rn cDNA clone and established that the derived mouse IL-1rn protein sequence is highly homologous to the human counterpart molecule. Mouse IL-1rn mRNA may be induced in P388D1 monocytic cells with PMA and in mouse liver in vivo by development of an experimental inflammation via s.c. injection of azocasein. This latter observation implies the existence of an autocrine hepatic negative feedback loop that down-regulates the acute phase response and is itself induced at the same time as the major acute-phase proteins. The mouse Il 1rn gene was mapped to the proximal region of chromosome 2 between the centromere and Spna2; the other known members of the mouse IL-1 gene family, Il 1a and Il 1b, both map to the same chromosome, although not in close linkage.
Analysis of the binding site architecture of monoclonal antibodies to morphine by using competitive ligand binding and molecular modeling.
Authors: Kussie P H , Anchin J M , Subramaniam S , Glasel J A , Linthicum D S 
Published: December 2022

Abstract
The structural features of mAb directed against the opiate morphine were analyzed by using competitive ligand analog-binding studies, examination of the V region amino acid sequence, and computer-aided molecular modeling of the fragment V region. The antibody response in BALB/c mice to morphine is relatively restricted, in that all of the mAb examined in this study contained the same lambda L chain and very similar H chain V regions. A three-dimensional model of the antimorphine-binding site was constructed by using computational and graphic display techniques. Each of the six complementary-determining regions was constructed by using fragment replacement methods employing canonical loop conformations of known "parent" structures. Experimental competitive ligand-binding data and theoretical modeling suggest that a charged glutamate residue at position H:50 and aromatic side chains of residues H:33W, H:47W, H:58F, H:95W, H:101iY, and L:91W are key features in ionic and hydrophobic interactions with the ligand. This study represents the first use of theoretical and experimental modeling techniques to describe the Ag-binding site of a mouse fragment V region containing a lambda L chain.
Binding of IgG containing immune complexes to human neutrophil Fc gamma RII and Fc gamma RIII induces actin polymerization by a pertussis toxin-insensitive transduction pathway.
Authors: Brennan P J , Zigmond S H , Schreiber A D , Smith E R , Southwick F S 
Published: December 2022

Abstract
The ability of a phagocytic stimulus, rabbit IgG anti-BSA/BSA immune complexes, to increase the F-actin content of human polymorphonuclear leukocytes was quantitated by flow cytometry following staining with nitrobenzoxadiazole-phallacidin. A significant rise in F-actin assembly was induced by addition of 5 micrograms/ml immune complex. Concentrations of immune complex of more than 200 micrograms/ml caused a maximal (approximately twofold) increase in F-actin content. After a delay of 5 s, the F-actin levels rose and reached maximum levels by 60 s after adding immune complexes. The twofold elevation in F-actin persisted for up to 60 min. Both anti-Fc gamma RII and anti-Fc gamma RIII mAb blocked immune complex stimulated actin polymerization. Exposure to pertussis toxin failed to affect the rate or extent of immune complex-induced actin polymerization. Cells incubated with immune complexes and then lysed with Triton had an increased number of sites able to nucleate actin polymerization. These findings suggest that immune complex binding to both polymorphonuclear leukocytes Fc gamma RII and Fc gamma RIII is required for actin filament assembly and that the induction of assembly occurs via transduction pathways that differ from those used by chemoattractants. As with adhesion this phagocytic stimulus induces actin assembly by a pertussis toxin insensitive pathway and produces a rise in actin filament content that persists for prolonged periods of time.
Rat CD16 is defined by a family of class III Fc gamma receptors requiring co-expression of heteroprotein subunits.
Authors: Farber D L , Sears D W 
Published: December 2022

Abstract
Rat CD16 is defined here by a family of highly homologous class III Fc gamma receptor isoforms. Northern blot and polymerase chain reaction analysis indicate that multiple rtFc gamma RIII alpha isoforms are expressed by rat NK and macrophages contrasting the expression of a single class III receptor isoform by human and mouse NK and macrophages. Analysis of genomic Southern blots and splice variants identified by polymerase chain reaction suggests the existence of several homologous rat Fc gamma RIII alpha genes organized similar to human and mouse class III receptor genes. All rat Fc gamma RIII alpha isoform protein sequences have conventional transmembrane insertion sequences containing the unique LFAVDTGL motif conserved in all other class III Fc gamma and Fc epsilon RI alpha receptor sequences. A model is proposed for the protein-protein interactions between this sequence and the transmembrane sequences of two heteroprotein subunits, Fc epsilon RI gamma and CD3 zeta, known to interact with human and mouse class III receptors. Rat NK, monocytes, and neutrophils were all found to express transcripts for both of these subunits, whereas rat macrophages express only Fc epsilon RI gamma subunit transcripts. Furthermore, the Fc epsilon RI gamma subunit was found to promote the cell surface expression of rtFc gamma RIII alpha isoforms in transfected COS cells.
Genetic diversity at class II DRB loci of the primate MHC.
Authors: Gyllensten U , Sundvall M , Ezcurra I , Erlich H A 
Published: December 2022

Abstract
The evolution of polymorphism at loci encoding the beta-chains of the MHC class II DR Ag was studied in primates by DNA amplification (polymerase chain reaction). Phylogenetic analysis of 63 DRB sequences from the polymorphic second exon (first domain) of nonhuman primates and 53 human sequences indicates the presence of five DRB loci in primates, derived from a DRB1-like ancestral locus over 20 million yr ago. Many of the allelic types at the DRB1 locus predate the divergence of hominoids (5 million yr ago) and some (DR4, DR3, 5, 6) predate the divergence of Old world monkeys and hominoids (20 million yr ago). The DRB3 locus appears to have arisen before the divergence of hominoids on an ancestral DRB1 lineage. The DRB2 and DRB5 loci were generated more than 20 million yr ago and the DRB4 locus more than 5 million yr ago. The DRB2 locus, a pseudogene in humans, is polymorphic in the nonhuman primates.