bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effect of polymorphism at HLA-DR1 beta-chain positions 85 and 86 on binding and recognition of DR1-restricted antigenic peptides.
Authors: Newton-Nash D K , Eckels D D 
Published: December 2022

Abstract
The valine-glycine dimorphism at position 86 of the DR beta-chain exhibited by most DR alleles has been shown to affect peptide binding. We demonstrate that DR1-restricted antigenic peptides differ in the extent to which binding is affected by amino acid substitution at positions 85 and 86 of the DR1 beta-chain. Binding of peptides derived from influenza hemagglutinin (HA306-320) and tetanus toxin (TT830-843) but not influenza matrix protein (MP19-31) was diminished on cells expressing DR1 beta-chains encoded by DRB1*0102 relative to DRB1*0101. The presence of tyrosine within HA306-320 and TT830-843 vs leucine within MP19-31 at a single DR contact position was revealed by alignment of the peptides according to a DR-binding motif. HA306-320 bearing leucine at this position (HA 306-320L309) bound to DR1 possessing either DRB1*0101- or DRB1*0102-encoded beta-chains suggesting that DR residues may discriminate among peptides based upon amino acid identity at a single position within the peptide. Furthermore, whereas all HA306-320-specific T cell clones recognized HA306-320L309 in the context of DR1 molecules possessing DRB1*0102-encoded beta-chains, some T cell clones failed to recognize HA306-320L309 in the context of DR1 molecules possessing DRB1*0101-encoded beta-chains. These results suggest that peptide conformation may also be affected by amino acid substitution at positions 85 and or 86 of the DR1 beta-chain.
Herpes simplex virus class I-restricted peptide induces cytotoxic T lymphocytes in vivo independent of CD4+ T cells.
Authors: Vasilakos J P , Michael J G 
Published: December 2022

Abstract
Cytotoxic T cells were induced in vivo by immunizing C57BL/6 mice with a single dose of a short synthetic peptide representing amino acid residues 497-507 from HSV-1 glycoprotein B. Primed lymph node cells did not require in vitro boosting with peptide and APC for CTL detection. The CTL were CD8+ and H-2b restricted. They were capable of lysing target cells exogenously sensitized with peptide or endogenously processed glycoprotein B. Virus-primed CTL produced an anamnestic response in vivo upon peptide challenge, indicating that peptide-specific CTL may be relevant to infection. The requirement of CD4+ T cells for CD8+ CTL activation was investigated by depleting CD4+ cells in vivo with GK1.5 mAb. CD4+ T cell depletion did not abrogate CTL generation. These results suggest that glycoprotein B peptide 497-507 activates CD8+ CTL in vivo in a manner independent of CD4+ T cells. This is the first study in which a class I-restricted peptide derived from a HSV protein was used to activate CTL in vivo, and in which a synthetic peptide was shown to activate CTL independent of CD4+ T cell help. Our data are relevant to viral vaccine development and to processing and presentation of viral epitopes.
The oligomeric nature of the murine Fc epsilon RII/CD23. Implications for function.
Authors: Dierks S E , Bartlett W C , Edmeades R L , Gould H J , Rao M , Conrad D H 
Published: December 2022

Abstract
The low affinity receptor for IgE (Fc epsilon RII/CD23) is a type II integral membrane protein with an extracellular C-terminal region homologous to C-type animal lectins. Immediately adjacent to this lectin homology region is a sequence that is predicted to form an alpha-helical coiled-coil stalk leading to dimer or trimer formation. This provides an explanation for the known self-associative capacity for the Fc epsilon RII. In this study the self-association to a trimer or tetramer is shown with rFc epsilon RII by chemical cross-linking and affinity purification on IgE columns. The data indicate that only the oligomeric form of Fc epsilon RII has sufficient affinity/avidity to bind to an IgE adsorbent. In contrast, Fc epsilon RII that is purified using anti-Fc epsilon RII mAb adsorbents has largely lost its capacity to bind IgE, as well as its capacity to self-associate, indicating that IgE recognizes the oligomeric form of the Fc epsilon RII. This phenomenon was further examined by performing detailed binding analysis of the mouse IgE/Fc epsilon RII interaction. A biphasic binding curve with high (2-7 x 10(7) M-1) and low (2-7 x 10(6) M-1) affinity binding was seen. Fc epsilon RII mutants were prepared that lack one or more of the 21 amino acid homologous repeat domains in the stalk region of the molecule. These mutant Fc epsilon RII molecules bound IgE with only a single low affinity (5-10 x 10(6) M-1). In addition, cross-linking analysis of one of these mutants demonstrated that it does not exhibit the receptor self-association seen for the intact Fc epsilon RII. Two chimeric Fc epsilon RII molecules were prepared having the mouse Fc epsilon RII lectin homology (carboxyl-terminal) region and the stalk region of either the related human Fc epsilon RII or the corresponding domain of Ly-49. Chimeric molecules using the former (alpha-helical coiled-coil) stalk supported normal binding of IgE although the Ly-49/Fc epsilon RII chimera failed to bind IgE. Taken together, the results indicate that high (approximately 10(8) M-1) affinity IgE binding results from interaction of multiple lectin domains with (presumably) symmetrical sites on the IgE molecule. Specificity for IgE is determined by the lectin domain although the binding avidity is determined by oligomerization through the coiled coil stalk.
Hydrolysis of myelin basic protein in myelin membranes by granzymes of large granular lymphocytes.
Authors: Vanguri P , Lee E , Henkart P , Shin M L 
Published: December 2022

Abstract
Immune-mediated demyelination initially manifests as a separation of myelin lamellae followed by loss of myelin proteins and eventual loss of myelin membranes. Myelin basic protein, one of the major structural proteins of myelin, is highly vulnerable to various proteases derived from diverse cell types. Killer lymphocytes such as CTL, in addition to other immune effectors, have been implicated in inflammatory demyelination. In addition to a pore forming peptide, the granules of CTL and large granular lymphocytes (LGL) contain a number of serine esterases collectively called as granzymes. We studied the effect of these granule enzymes on myelin and found that LGL granule-extracts (LGL-g) hydrolyzed MBP in myelin membranes. LGL-g also cleaved purified MBP at neutral pH in a Ca2+ independent manner and this hydrolysis was inhibited by serine esterase inhibitors. In addition, absorption of LGL-g with antigranzyme A significantly reduced MBP hydrolysis. These findings implicated the granzymes in LGL-g, especially granzyme A, as the agent causing MBP degradation. Inasmuch as activation of CTL in the vicinity of myelinated axons can lead to granule exocytosis, hydrolysis of MBP by granzymes may be a significant event in myelin destruction.
Involvement of IFN-gamma and transforming growth factor-beta in graft-vs-host reaction-associated immunosuppression.
Authors: Huchet R , Bruley-Rosset M , Mathiot C , Grandjon D , Halle-Pannenko O 
Published: December 2022

Abstract
The mechanisms of the suppressive activity of spleen cells from mice undergoing a graft-vs-host reaction (GVH) to non-H-2 histocompatibility Ag were investigated. In our model GVH is induced by injecting bone marrow and spleen cells from B10.D2 (H-2d Mlsb) donors into lethally irradiated (DBA/2 x B10.D2)F1 (H-2d/d Mlsa/b) recipients that differ only with regard to non-H-2 Ag. GVH spleen cells inhibit the mitogenic responses to Con A and LPS, as well as the anti-bromelain-treated mouse RBC (Br-MRBC) antibody response. This suppression was nonspecific and non-H-2-restricted and was not modified after treatment with anti-Thy-1 plus C. Conversely it was abrogated after treatment with L-leucyl methyl ester. These features permitted the identification of non-T cell, L-leucyl methyl ester-sensitive, cells involved in this type of suppression. The suppression mediated by GVH spleen cells was linked to the activity of IFN-gamma and transforming growth factor-beta 1 (TGF-beta 1) (TGF-beta 1 was found to be synthesized by GVH spleen T cells). mAb to IFN-gamma abrogated the suppression of the mitogenic response to Con A and the anti-Br-MRBC response and slightly reversed the suppression of the mitogenic response to LPS. Anti-TGF-beta 1 antibody partially abrogated the suppression of the mitogenic response to LPS and totally abrogated that of the anti-Br-MRBC response but left unmodified the suppression of the mitogenic response to Con A. These results are discussed within the framework of the mechanisms underlying the immunosuppression associated with GVH.
Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta.
Authors: Lee S C , Liu W , Dickson D W , Brosnan C F , Berman J W 
Published: December 2022

Abstract
As part of a study on the role of cytokines in central nervous system development and dysfunction, we determined the pattern of cytokine production in highly purified cultures of microglia and astrocytes isolated from second-trimester human fetal brains. Levels of TNF-alpha, IL-1 beta, and IL-6 mRNA and protein were determined by Northern blot analysis and ELISA before and after stimulation with LPS, TNF-alpha, or IL-1 beta. In microglia, LPS induced mRNA for all three cytokines. High protein levels of IL-6 and TNF-alpha were also found in the medium, whereas IL-1 beta protein was mostly cell associated. IL-1 beta also induced message for all three cytokines, in the rank order of IL-1 beta &gt; IL-6 &gt; TNF-alpha. TNF-alpha induced mRNA and protein for IL-1 beta but not for TNF-alpha or IL-6. In contrast, LPS failed to stimulate either mRNA or protein expression for any of the three cytokines in astrocytes. On the other hand, IL-1 beta provided a strong stimulus for astrocytes. IL-1 beta induced mRNA and protein for both TNF-alpha and IL-6, but the kinetics of the response differed for the two cytokines. TNF-alpha mRNA and protein levels peaked early (at 4 h and 16 h, respectively) and were undetectable by 72 h, whereas IL-6 mRNA peaked later (at 16 h) and protein levels continued to accumulate in the medium through 72 h. IL-1 beta did not induce IL-1 beta mRNA or protein in astrocytes. TNF-alpha did not induce expression of any of the cytokines in astrocytes. In conclusion, our results demonstrate that cytokine production can be induced in human fetal microglia and astrocytes but that the stimuli for induction differed significantly for the two cell types. Whereas LPS was a potent stimulus for microglia, astrocytes primarily responded to IL-1 beta. The data further suggest that microglia may be key regulators of astrocyte response, working primarily through the expression of cell-associated IL-1 beta.
Sequence analysis and antigenic cross-reactivity of a venom allergen, antigen 5, from hornets, wasps, and yellow jackets.
Authors: Lu G , Villalba M , Coscia M R , Hoffman D R , King T P 
Published: December 2022

Abstract
Ag 5 is a major allergen of vespid venom. The complete amino acid sequences of Ag 5 from two species each of hornets (Dolichovespula arenaria and maculata), wasps (Polistes annularis and exclamans), and yellow jackets (Vespula maculifrons and vulgaris) have been determined by amino acid sequencing and/or cDNA cloning. The sequence data reveal several conserved and variable regions for vespid Ag 5. The conserved regions show greater sequence similarity than do the less conserved regions to a family of proteins from human, mouse, and rat testis and to a class of pathogenesis-related proteins from tobacco and tomato leaves. Tests in the murine system for both T and B cell responses demonstrate a high degree of cross-reactivity of hornet Ag 5 with wasp or yellow jacket Ag 5 and a low degree of cross-reactivity of yellow jacket Ag 5 with wasp Ag 5. This pattern of cross-reactivity is in the same order as their sequence similarity.
Separation of T helper 1 clone cytolysis from proliferation and lymphokine production using analog peptides.
Authors: Evavold B D , Sloan-Lancaster J , Hsu B L , Allen P M 
Published: December 2022

Abstract
In this report, we investigate the activation of Th1 clones using altered TCR ligand. By changing the immunogenic peptide, cytolytic function can be separated from proliferative and lymphokine responses. These three responses were examined and dissected in two Th1 clones using analogs of the murine hemoglobin [Hb(64-76)] peptide. This analysis was focused on amino acids in the immunogenic peptide that were possible T cell contact residues. Typically, several amino acids were identified as critical contact residues for a Th1 proliferative response. An examination of lymphokine production (IFN-gamma or IL-3) revealed the same pattern of response to the analog peptides indicating that the proliferative and lymphokine responses were directly related. However, for cytolysis, fewer amino acid residues were identified as critical contact residues for effector function. Thus, some altered peptide ligands allowed the disassociation of the cytolytic function from the proliferative and lymphokine responses in Th1 clones. To extend these findings, the activation of T cell hybridomas created from the Th1 clones were similarly examined using the altered TCR ligands. The lymphokine response (IL-2) of the T cell hybridomas identified the same critical amino acids as did the cytolytic response of the Th1 clones. Thus, analog peptides partially activated the Th1 clones such that cytolysis occurred independent from proliferative and lymphokine responses.
Cytolytic activity of murine CD4+ T cell clones correlates with IFN-gamma production in mouse strains having a BALB/c background.
Authors: McKisic M D , Lancki D W , Fitch F W 
Published: December 2022

Abstract
CD4+ murine T cell clones were derived from various strains of mice, and their pattern of lymphokine secretion and cytolytic activity was compared. Limiting dilution cultures were established with lymph node cells from mice sensitized with OVA. Alloreactive CD4+ T cell clones also were derived in limiting dilution cultures prepared with naive BALB/c-H-2dm2 lymph node cells stimulated with irradiated BALB/c splenocytes. A total of 24 days elapsed between establishment of cultures and analysis of lymphokine production and cytolytic activity. Cytolytic capacity was assessed by using target cells that had been pulsed with Ag or coated with anti-CD3 mAb. We observed that: 1) the frequency of OVA-reactive T cells from various mouse strains was approximately the same; 2) both Th1 and Th2 cells as well as cells not encompassed within these categories could be lytic if derived from DBA/2, B10.D2, B10.A, C57BL/10, or C57BL/6 mice; and 3) the vast majority of CD4+ cloned T cells derived from BALB/c, BALB/c-H-2dm2, BALB.B, or BALB.K that did not produce IFN-gamma (including Th2 cells) did not exhibit cytolytic activity, whereas most clones derived from these strains that produced IFN-gamma were cytolytic. These observations indicate that both Th1 and Th2 cells from several mouse strains express cytolytic activity. Such cytolytic activity was not restricted to clones maintained in long term cultures. However, genes outside the MHC appeared to regulate the cytolytic activity of T cells. In particular, CD4+ T cell clones which did not produce IFN-gamma were not cytolytic when they were derived from BALB/c mice and mutant or MHC congenic inbred mice having a BALB background. Cytolytic activity of CD4+ T cells, in addition to the pattern of lymphokine production, may be important in graft rejection and in immune responses to infectious diseases.
Picolinic acid, a catabolite of L-tryptophan, is a costimulus for the induction of reactive nitrogen intermediate production in murine macrophages.
Authors: Melillo G , Cox G W , Radzioch D , Varesio L 
Published: December 2022

Abstract
In this study we investigated the effects of picolinic acid, a catabolite of L-tryptophan, on the production of L-arginine-derived reactive nitrogen intermediates in the murine macrophage cell line ANA-1. ANA-1 macrophages did not produce nitrite (NO2-) constitutively, but accumulated detectable levels of NO2- on exposure to IFN-gamma. Picolinic acid, although ineffective by itself, augmented IFN-gamma-induced NO2- production. The activity of picolinic acid was evident at 1 mM and reached its maximum at 4 mM. Picolinic acid also augmented the IFN-gamma-dependent expression of TNF-alpha mRNA, but did not appreciably affect the secretion of the TNF-alpha protein. Neutralizing concentrations of anti-TNF mAb completely abrogated IFN-gamma- and IFN-gamma plus rTNF-alpha-induced NO2- production in ANA-1 macrophages, but only decreased by approximately 50% the synergistic interaction between IFN-gamma and picolinic acid. Although IL-4 inhibited the expression of IFN-gamma plus picolinic acid-induced TNF-alpha mRNA and protein, it only partially suppressed picolinic acid-dependent NO2- production. Therefore, picolinic acid may affect NO2- production via both TNF-alpha-dependent and TNF-alpha-independent pathways. Overall, this study suggests that amino acid catabolites may be important for the activation and the expression of effector functions by murine macrophages, and provides the first evidence of a possible connection between tryptophan and arginine metabolism.
Contrasting effects of transforming growth factor-beta and IL-1 on the regulation of plasminogen activator inhibitors in human synovial fibroblasts.
Authors: Hamilton J A , Wojta J , Gallichio M , McGrath K , Filonzi E L 
Published: December 2022

Abstract
TGF-beta increased in a dose-dependent manner the production of plasminogen activator inhibitor-1 (PAI-1) in cultured human synovial fibroblast-like cells, as measured by ELISA. Significant increases in PAI-1 were first detected in cell supernatants within 4 h after cytokine addition. Increases were also observed in PAI-1 mRNA expression. IL-1 suppressed these increases in PAI-1 Ag and mRNA. In contrast, when PAI-2 levels were measured by ELISA, TGF-beta did not raise them but inhibited slightly the enhancement caused by IL-1 of PAI-2 Ag and mRNA. Therefore TGF-beta selectively stimulates the formation of one PAI; TGF-beta and IL-1 have opposing effects on PAI-1 and PAI-2 synthesis in the synovial cells. These findings are proposed to help define the control of fibrinolysis and tissue remodeling in the rheumatoid synovium.
Mechanism of release of soluble forms of tumor necrosis factor/lymphotoxin receptors by phorbol myristate acetate-stimulated human THP-1 cells in vitro.
Authors: Hwang C , Gatanaga M , Granger G A , Gatanaga T 
Published: December 2022

Abstract
The mechanism involved in the release of the soluble forms of 55 and 75 kDa TNF and lymphotoxin (LT) membrane receptors was studied in a continuous human monocytic cell line, THP-1, in vitro. THP-1 cells were found to spontaneously release soluble forms of both 55 and 75 kDa TNF/LT receptors. Release was up-regulated by PMA, and optimal release was achieved at 10(-8) M PMA. Serine protease inhibitors such as PMSF,3,4 dichloroisocoumarin, N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) were found to inhibit the production of both soluble TNF/LT receptors. PMSF (2 mM) also blocked receptors shedding from paraformaldehyde-fixed THP-1 cells coincubated with conditioned media from PMA-stimulated THP-1 cells. Colchicine at 1 and 10 microM stimulated the production of both soluble TNF/LT receptors, but the PMA-induced release of both soluble TNF/LT receptors was inhibited. It appears that the PMA-induced release of soluble TNF/LT receptors involves serine proteases in the extracellular space where the soluble parts of the TNF/LT receptors are cleaved directly off the cell membrane.
Developmental regulation of IL-4, IL-2, and IFN-gamma production by murine peripheral T lymphocytes.
Authors: Adkins B , Ghanei A , Hamilton K 
Published: December 2022

Abstract
Lymph node T cells from naive, 4-day-old neonatal mice resemble activated adult T cells in that they produce low levels of IL-2 but high levels of IL-4 in response to anti-CD3 stimulation in vitro. Herein, we show that the capacity for high level IL-4 production is rapidly lost in the early postnatal period. A decline is first evident at 5 days postbirth. By 6 days postbirth, T cells secrete IL-4 at low levels, similar to those produced by T cells from naive, adult animals. In contrast, the acquisition of high, adultlike IL-2 or IFN-gamma production does not occur until approximately 6 wk of life. Thus, the loss of high level IL-4 production and the acquisition of high level IL-2 and IFN-gamma production are distinct developmental events, occurring at widely separated intervals. There are two phases in the transition to adultlike IL-2 production. In the early neonatal period, the underproduction of IL-2 appears to be due to a combination of intrinsic nonresponsiveness to CD3-mediated stimulation and the production of a soluble inhibitor of IL-2 production. The inhibitory activity required the presence of IL-4 because neutralizing anti-IL-4 antibody completely eliminated inhibition. Moreover, experiments using rIL-4 showed that IL-4 alone was sufficient to dramatically inhibit IL-2 production by T cells from naive, adult animals in a primary stimulation. Between 4 to 5 days and 6 wk of life, the underproduction of IL-2 and IFN-gamma appears to result solely from a lowered responsiveness of the T cells. Thus, the progression to adultlike lymphokine production involves a combination of changes in the types of lymphokines produced and in the magnitude of the response to activation signals.
Presentation of cytosolic antigen by HLA-DR requires a function encoded in the class II region of the MHC.
Authors: Malnati M S , Ceman S , Weston M , DeMars R , Long E O 
Published: December 2022

Abstract
The processing pathway for the MHC class II-restricted presentation of endogenous cytosolic Ag is distinct from the class I pathway since a cytosolic form of the influenza virus A hemagglutinin, expressed by a recombinant vaccinia virus, was presented by HLA-DR in a B cell mutant lacking the TAP1 subunit of the transporter for Ag presentation (TAP). In this report, two additional B cell mutants have been used to define the requirements of this TAP1-independent processing pathway. The first mutant, .61, lacks expression of both TAP1 and TAP2 genes, and of both LMP2 and LMP7 genes encoding proteasome subunits. As expected, class I-restricted presentation of the influenza virus matrix protein was totally deficient in mutant .61. In contrast, class II-restricted presentation of both the natural cytosolic matrix and the engineered cytosolic hemagglutinin proteins was functional in mutant .61. Thus, presentation of cytosolic Ag by class II molecules is independent of both TAP subunits and of the two MHC-encoded proteasome subunits. However, this endogenous processing pathway is dependent on at least one other function encoded in the class II region of the MHC as demonstrated with the second mutant, .174, in which a large deletion eliminates all expressed class II genes. Mutant .174 transfected with HLA-DR1 genes was previously shown to be defective in the presentation of exogenous Ag but normal in the presentation of short exogenous peptides. We show here that .174(DR1) is also defective in the presentation of cytosolic matrix and hemagglutinin proteins. This similar requirement for the class II-restricted presentation of either cytosolic Ag or internalized exogenous Ag suggests that both forms of Ag are ultimately targeted to the same cellular compartment for association with class II molecules.