bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introduction of T cell receptor (TCR)-alpha cDNA has differential effects on TCR-gamma delta/CD3 expression by PEER and Lyon-1 cells.
Authors: De Waal Malefyt R , Alarcon B , Yssel H , Sancho J , Miyajima A , Terhorst C P , Spits H , De Vries J E 
Published: December 2022

Abstract
A TCR heterodimer composed of a TCR gamma-chain and a TCR delta-chain was found to be expressed in association with CD3 by a small population of human peripheral blood T cells, thymocytes, and certain leukemic T cell lines. The leukemic T cell lines PEER and Lyon-1 express such a TCR-gamma delta/CD3 complex at the cell surface. In addition, PEER and Lyon-1 cells transcribe a productively rearranged TCR-beta gene. Introduction of TCR alpha-chain cDNA of human or murine origin resulted in cell surface expression of a TCR-alpha beta/CD3 complex on PEER and Lyon-1 cells. The expression of the TCR-gamma delta/CD3 complex on PEER cells was not affected by introduction of TCR-alpha cDNA. In contrast, introduction of a TCR-alpha cDNA and expression of the TCR-alpha beta/CD3 complex in Lyon-1 cells resulted in the disappearance of the TCR-gamma delta/CD3 complex. These data were confirmed by indirect immunofluorescence, at the protein level and by gene expression analysis. Triggering of the TCR-alpha beta/CD3 complexes by anti-CD3 mAb or anti-TCR mAb resulted in increased internal Ca2+ levels, indicating that these receptors were functional in signal transduction. These results indicate that, besides TCR gene rearrangements, membrane expression of TCR-alpha beta heterodimers may be important in regulating TCR-gamma delta cell surface expression.
Mixed IgA-IgG aggregates as a model of immune complexes in IgA nephropathy.
Authors: Waldo F B , Cochran A M 
Published: December 2022

Abstract
Patients with IgA nephropathy have circulating immune complexes containing IgA, IgG, and C3. We have mixed human IgG and IgA1 and heated them to form mixed aggregate. On sucrose density gradients IgG aggregates were 11 to 19S whereas IgA aggregates were either 11S or greater than 19S. Mixed aggregates had both an 19 and 11 S peak. The isoelectric point of aggregates with only IgG was 7 to 9 and of only IgA 4.5 to 5.5. The isoelectric point of mixed aggregates decreased as the percent IgA increased. IgG aggregates mixed with normal human serum caused 30% C3 activation (20 min, 37 degrees C) whereas IgA aggregates causes no activation. There was a linear decrease in C3 activation as the percent IgA increased. Mixed aggregates that contained either radiolabeled IgG or IgA were mixed with normal human serum (1 h, 37 degrees C) and then solubilized, reduced, and separated by 10% SDS-PAGE. Heavy m.w. bands, consistent with covalent bonding of C3b and C3bi to Ig H chain were only seen in lanes with labeled IgG. This was confirmed by Western blot analysis. A human dimeric IgA1 myeloma protein with rheumatoid factor activity was also studied. It caused 15% alternative pathway C3 activation but did not fix C3 to its H chain. Binding of aggregates (+/- C3) to E was tested. Aggregates with IgG C3 bound but IgA (+/- C3) did not. Addition of greater than 10% IgA to an IgG-C3 aggregate inhibited E binding. We conclude that IgG in mixed aggregates is the site of C3 fixation. In contrast, IgA does not fix C3 but instead lowers the isoelectric point, increases the size and inhibits binding to E. These properties would inhibit clearance and promote mesangial deposition and local C activation.
Generation and characterization of hamster monoclonal antibodies that neutralize murine tumor necrosis factors.
Authors: Sheehan K C , Ruddle N H , Schreiber R D 
Published: December 2022

Abstract
mAb to murine TNF (MuTNF) were produced after immunization of Armenian hamsters with purified, Escherichia coli-derived rMuTNF-alpha. Antibody produced from clone TN3-19.12, was purified and was found to inhibit 100% of the lytic activity of either recombinant or natural MuTNF-alpha at an antibody input of 25 ng/U. TN3-19.12 also inhibited all the lytic activity in culture supernatants from a variety of T cell sources, including activated T cell clones and T cell hybridomas (all of which expressed high levels of TNF-alpha and TNF-beta (lymphotoxin, LT) mRNA). Western blot analysis was used to document the physical form(s) of MuTNF recognized by TN3-19.12. Recombinant and macrophage-derived TNF displayed identical patterns of a single band with Mr 17 kDa. In contrast, T cell culture supernatants exhibited patterns consisting of two bands with Mr 17 and 24.7 kDa. The higher m.w. form was glycosylated based on its sensitivity to n-glycanase and displayed a m.w. consistent with that of TNF-beta (LT). These data suggest that TN3-19.12 recognizes both MuTNF-alpha and MuTNF-beta (LT). Monoclonal TN3-19.12 and polyvalent rabbit anti-rTNF were used to establish a MuTNF-specific ELISA capable of detecting picogram quantities of recombinant or natural TNF. This assay was used to detect TNF in the sera of mice challenged with a lethal dose of LPS. Peak TNF serum levels of 11 ng/ml were observed in these animals 90 min after i.p. LPS administration and then rapidly declined to near base line levels by 3 h. These values were confirmed by quantitating levels of TNF functional activity in the same samples. TN3-19.12 injected into mice subsequently treated with LPS prevented the detection of TNF in the circulation by either assay and protected mice from the lethal effects of endotoxin shock. Thus, TN3-19.12 effectively neutralizes endogenously produced TNF in vivo.
Carbohydrates on human Fc gamma receptors. Interdependence of the classical IgG and nonclassical lectin-binding sites on human Fc gamma RIII expressed on neutrophils.
Authors: Kimberly R P , Tappe N J , Merriam L T , Redecha P B , Edberg J C , Schwartzman S , Valinsky J E 
Published: December 2022

Abstract
To explore the molecular basis for the ability of aggregated IgG to block the phagocytosis by human polymorphonuclear leukocytes of Con A-opsonized E and of nonopsonized Escherichia coli with mannose-binding adhesins, we examined specific aspects of the glycoprotein structure of both the 40- to 43-kDa receptor for the Fc portion of IgG (Fc gamma RII) and the 50- to 78-kDa receptor for the Fc portion of IgG (Fc gamma RIIIPMN) from human polymorphonuclear leukocytes. Fc gamma RIIIPMN isolated by both mAb and ligand affinity chromatography, but not Fc gamma RII, binds Con A in Western blots. This binding is specifically inhibitable by alpha-methylmannoside. Digestion of Fc gamma RIIIPMN by recombinant endoglycosidase H, which is specific for high mannose-type (Con A-binding) oligosaccharides, alters the epitope recognized by mAb 3G8 in or near the IgG ligand-binding site of the receptor. Similarly, the ability of Fc gamma RIIIPMN to bind human IgG ligand is sensitive to endoglycosidase H digestion. Our data indicate that ligands other than the classical IgG opsonins can bind to human Fc gamma RIIIPMN per se through lectin-carbohydrate interactions. Furthermore, Fc gamma RIIIPMN contains a high mannose type oligosaccharide chain which contributes importantly to the integrity of the classical IgG ligand-binding site. Thus, specific glycosylations of the receptor are important for both classical and nonclassical engagement of Fc gamma RIII and may play a role in determining the properties of the ligand-binding site.
Diversity and diversification of HLA-A,B,C alleles.
Authors: Parham P , Lawlor D A , Lomen C E , Ennis P D 
Published: December 2022

Abstract
The nucleotide sequences encoding 14 HLA-A,B,C and 5 ChLA-A,B,C molecules have been determined. Combining these sequences with published data has enabled the polymorphism in 40 HLA-A,B,C and 9 ChLA-A,B,C alleles to be analyzed. Diversity is generated through assortment of point mutations by recombinational mechanisms including gene and allelic conversions. The distribution and frequency of silent and replacement substitutions indicate that there has been positive selection for allelic diversity in the 5' part of the gene (exons 1 to 3) and for allelic homogenization and locus specificity in the 3' part of the gene (exons 4 to 8). These differences may correlate with the lengths of converted sequences in the two parts of the gene and frequency of the CpG dinucleotide. Locus-specific divergence of HLA-A,B, and C demonstrates that recombinational events involving alleles of a locus have been more important than conversion between loci. This contrasts with the predominance of gene conversion events in the evolution of mutants of the H-2Kb gene. However, a striking example of gene conversion involving HLA-B and C alleles of an oriental haplotype has been found. Comparison of human and chimpanzee alleles reveals extensive sharing of polymorphisms, confirming that diversification is a slow process, and that much of contemporary polymorphism originated in ancestral primate species before the emergence of Homo sapiens. There is less polymorphism at the HLA-A locus compared to HLA-B, with greater similarity also being seen between HLA-A and ChLA-A alleles than between HLA-B and ChLA-B alleles. Although greater diversity is seen in the 5' "variable" exons of HLA-B compared to HLA-A, there is increased heterogeneity in the 3' "conserved" exons of HLA-A compared to HLA-B.
Human endothelial cells prolong eosinophil survival. Regulation by cytokines and glucocorticoids.
Authors: Lamas A M , Marcotte G V , Schleimer R P 
Published: December 2022

Abstract
Many recent studies have established the eosinophil as an active proinflammatory participant in a variety of disease states, most notably in allergic and helminthic disorders. In order to understand the effector role of eosinophils, factors which promote a selective eosinophilic infiltrate must be delineated. Eosinophil adherence to vascular endothelium is the first step in the formation of such an infiltrate. However, studies thus far have failed to identify factors which selectively activate the adherence of eosinophils. We have therefore speculated that the selective enrichment of eosinophils may result from nonselective recruitment of several leukocyte types combined with the production of local factors that promote the survival of eosinophils and not of other cells. We report that endothelial cell-conditioned medium selectively prolongs eosinophil survival up to 6 days in culture in a dose- and time-dependent manner. Stimulation of human vascular endothelial cells with IL-1 caused an increase in the generation of eosinophil survival-promoting activity, whereas stimulation with platelet-activating factor did not. Supernatants from human vascular endothelial cells cultured for 48 h in the presence of the glucocorticoid, dexamethasone, were less active in promoting eosinophil survival than control supernatants. These results suggest that factors produced locally in the vascular microenvironment may selectively promote eosinophil survival and may be under the regulation of cytokines and glucocorticoids.
Indiscriminate representation of VH-gene families in the murine B lymphocyte responses to Trypanosoma cruzi.
Authors: Minoprio P , Andrade L , Lembezat M P , Ozaki L S , Coutinho A 
Published: December 2022

Abstract
The utilization of the nine major homology families of VH-genes was quantitated in the B lymphocyte response to Trypanosoma cruzi infection of C57BL/6 mice. Normal and infected mice at various times after parasite inoculation were compared for VH-gene distribution of CFU-B produced by activated blasts recovered from spleen and lymph nodes, and for relative hybridization of total spleen RNA with each of the family probes. T. cruzi infection results in large increases of splenic RNA in the various homology families, and the numbers of activated CFU-B, reflecting the massive B lymphocyte responses. In acute phase, all nine families are expressed in roughly the same proportions as in normal mice, whereas in chronic infection, B cells expressing S107 and 7183 VH-genes might be preferentially stimulated. These results establish the polyclonal nature of the host response to T. cruzi infection.
Differential expression of the class I MHC genes in the embryo and placenta during midgestational development in the mouse.
Authors: Hedley M L , Drake B L , Head J R , Tucker P W , Forman J 
Published: December 2022

Abstract
A sensitive RNase mapping technique was used to investigate the expression of individual class I mRNA in the embryo and placenta of the mouse from day 7.5 through day 13 of gestation. Transcripts of the H-2Kd and -Dd genes appeared in both placental and embryonic tissues as early as day 7.5 post coitum and continued to be expressed thereafter. In contrast, H-2Ld mRNA was barely detectable in embryonic RNA until day 18 of pregnancy, although it was present in placental RNA samples on days 10 to 13 of gestation. Qa-region genes demonstrated a different pattern of expression than H-2Dd, -Kd, and -Ld. Transcripts of Q7, one of the genes encoding Qa-2 surface Ag, were detected in the developing embryo on days 9 to 11 post coitum but decreased thereafter. However, Q7d transcripts were not detected in placental tissues at any stage. Q6 mRNA was not detected in any of the tissues, and Q10 mRNA was detected only in day 12 to 13 embryos, where expression is known to be restricted to the fetal liver. Transcripts from T13, a Tla-region gene, and D2d, a D-region gene, were not detected in any of the samples tested. This study has revealed a complex pattern of class I gene regulation both within the genes of the MHC and between the embryo and placental lineages during the midgestational stages of development.
Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis. VII. Responsiveness is associated with expression of a product(s) of the V beta 8 gene family present on the T cell receptor alpha/beta for antigen.
Authors: Cole B C , Kartchner D R , Wells D J 
Published: December 2022

Abstract
Mycoplasma arthritidis produces a potent soluble T lymphocyte mitogen (MAM) which is dependent upon accessory cells bearing the alpha-chain of the I-E molecule (E alpha). Lymphocytes from the RIIIS mouse strain which possess E alpha yet whose T cells fail to recognize the MAM-E alpha complex were shown not to express V beta 8.1, 8.2 or 8.3 gene products present on the TCR-alpha/beta by virtue of their lack of reactivity with the F23.1 mAb. Because lymphocytes from the congenic B10.RIII mouse strain reacted positively with F23.1, we examined the progeny from (RIIIS x B10.RIII)F1 x RIIIS backcross mice for cosegregation of lymphocytes expressing F23.1-reactive sites and ability to proliferate in response to MAM. Whereas lymphocytes of all mice responded to Con A, only lymphocytes from progeny expressing F23.1-reactive cells responded to MAM. Similar studies were conducted on progeny from the F23.1- SWR mouse which was backcrossed to (SWR x B10.RIII)F1 mice. Of the E alpha-bearing progeny, there was a direct correlation between lymphocyte expression of F23.1 determinants and ability to respond to MAM. These results established that MAM reactivity was dependent upon a product(s) of the V beta locus of the TCR-alpha/beta. Nodal and thymic lymphocytes cultured for 3 days in vitro with MAM exhibited clonal expansion of F23.1 and F23.2-reactive cells as compared with cultures treated with Con A. We also demonstrated that F23.1 and F23.2 mAb inhibited the ability of lymphocytes to proliferate in response to MAM but had little effect on responses to Con A. The combined data suggest that the MAM-E alpha complex can utilize a V beta 8 gene product(s) on the TCR-alpha/beta.
Molecular interactions required for triggering alloantigen-specific cytolytic T lymphocytes.
Authors: Kane K P , Sherman L A , Mescher M F 
Published: December 2022

Abstract
Affinity-purified class I proteins in detergent solution can be directly immobilized on plastic by a simple dilution procedure. The immobilized Ag retains its native structure and will trigger specific, TCR-mediated degranulation of cloned CTL. Stimulation of the response is dependent on the surface density of Ag, and displays a critical threshold density below which response does not occur. Individual clones differ with respect to the threshold density required for activation, but these differences are not large. With one exception, the cloned lines examined respond to Ag densities comparable to that found on normal allogeneic cells, and critical threshold densities varied over about a fourfold range. Coimmobilization of alloantigen and nonantigenic class I protein of a different specificity has the effect of decreasing the threshold density of alloantigen required for response to occur. This augmentation is specific for class I, coimmobilized class II protein does not affect responses, and is very likely mediated by Lyt-2 (CD8) interaction with nonpolymorphic determinants on the class I protein. Thus, class I alloantigen is the necessary and sufficient ligand for activation of most allogeneic CTL clones, and both TCR and Lyt-2 interactions contribute to the response. The results described here for effector CTL are compared with those previously found in examining the ligand requirements for activation of precursor CTL.
Processing and presentation of insulin. II. Evidence for intracellular, plasma membrane-associated and extracellular degradation of human insulin by antigen-presenting B cells.
Authors: Semple J W , Ellis J , Delovitch T L 
Published: December 2022

Abstract
To study the biochemistry of processing of a soluble protein Ag by an APC, we investigated how 125I-labeled human insulin (HI) is processed in situ by TA3 mouse hybridoma B cells. Fractionation of TA3 cells into their extracellular, plasma membrane-associated and intracellular compartments coupled with the use of HPLC enabled us to analyze several peptides derived from each compartment. One HI peptide found in all three compartments is composed of residues A1-A14 disulfide-linked to B7-B26 (A1-A14/B7-B26). The presence of this peptide in the extracellular compartment likely resulted from digestion of HI by an enzyme(s) released from the APC. Extracellular processing of radiolabeled HI was inhibited completely by unlabeled HI and N-ethylmaleimide, an inhibitor of a previously described insulin-specific protease, partially by lysozyme but not by BSA or OVA. This suggests that the enzyme involved in the extracellular processing of insulin is relatively insulin-specific and gives rise to the A1-A14/B7-B26 peptide. The processing of HI both at the plasma membrane and intracellularly was inhibited by chloroquine, monensin, and NH4Cl, suggesting that both intracellular pH changes and endocytic and exocytic events may be required for these compartments to process insulin. Kinetic analyses revealed that the processing of insulin into the A1-A14/B7-B26 peptide is first detected at the plasma membrane then intracellularly and finally in the extracellular compartment. This unlabeled A1-A14/B7-B26 peptide was purified from the extracellular compartment of TA3 APC by HPLC; when presented by TA3 APC this peptide effectively stimulated pork insulin (PI/I-Ad) specific Th cells to secrete IL-2. These data, taken together with the identification of another processed insulin peptide, A7-A11/B7-B26, have enabled us to elucidate the first steps in the biochemical pathway(s) of processing of insulin as an Ag in a B cell APC.
Soluble IL-2 receptor in AIDS. Correlation of its serum level with the classification of HIV-induced diseases and its characterization.
Authors: Honda M , Kitamura K , Matsuda K , Yokota Y , Yamamoto N , Mitsuyasu R , Chermann J C , Tokunaga T 
Published: December 2022

Abstract
By using a fluorescence sandwich ELISA, elevated IL-2R levels were detected in the sera from both HIV-infected hemophiliacs and other HIV-infected patients. The serum IL-2R levels were reflective of the classification of HIV-induced diseases by the Centers for Disease Control. Moreover, the IL-2R levels were negatively correlated most prominently with CD4 cell counts, with lymphocyte counts, and with a decrease in the CD4-CD8 ratio but not with either WBC counts or B cell counts. As striking elevations of serum IL-2R were noted in AIDS patients with group IVD infection, the serum IL-2R was purified sequentially by using size-exclusion HPLC, high-pressure chromatofocusing, and H48 affinity HPLC. The isoelectric point values of IL-2R were separated into 4.2 and 3.8, whereas the Mr was determined to be only 45 kDa by immunoprecipitation with H48 antibody followed by SDS-PAGE. However, production of cellular and supernatant IL-2R was not elevated in PBMC of patients with AIDS or in any of the 19 HIV-I- or HIV-II-infected cell line cells. In contrast, PBMC from patients with adult T cell leukemia and cell line cells that expressed human T cell lymphotropic virus -I or -II produced soluble IL-2R, constitutively. The mechanisms by which serum levels of IL-2R might be elevated in HIV-infected patients are discussed in comparison with that in adult T cell leukemia patients.
HLA class I-related impairment in IL-2 production and lymphocyte response to microbial antigens in reactive arthritis.
Authors: Inman R D , Chiu B , Johnston M E , Vas S , Falk J 
Published: December 2022

Abstract
The contribution of certain Gram-negative bacteria and host HLA class I Ag to the development of reactive arthritis (ReA)3 has strong epidemiologic support but the pathogenesis of the arthritis is unknown. An outbreak of Salmonella typhimurium afforded the opportunity to compare the immune response to the organism between those who developed ReA (ReA+, n = 11) with those who did not (ReA-, n = 12). Of the 11 ReA+ patients, 4 were B27-positive and 6 were B7-positive; of the ReA- patients none was B27- or B7-positive. The causative pathogen S. typhimurium phage 22 was used to examine PBL proliferation by [3H]thymidine incorporation. Impairment in lymphocyte response to S. typhimurium in ReA+ compared with ReA- was demonstrated by: i) lower stimulation index (1.9 +/- 0.3 for ReA+, 5.7 +/- 0.6 for ReA-, p less than 0.01); ii) lower in vitro Ig production; and iii) lower Ag-induced IL-2 production. Mixing experiments did not demonstrate a soluble suppressor factor in ReA+ supernatants. Thus, after infection with S. typhimurium there is an impairment in cellular immunity that has correlates in immunogenetic and clinical features of the infected population.
Synthetic peptide corresponding to a conserved domain of the retroviral protein p15E blocks IL-1-mediated signal transduction.
Authors: Gottlieb R A , Lennarz W J , Knowles R D , Cianciolo G J , Dinarello C A , Lachman L B , Kleinerman E S 
Published: December 2022

Abstract
We studied the mode of action of the synthetic peptide CKS-17, which is a heptadecapeptide homologous to a highly conserved region of the immunosuppressive retroviral envelope protein p15E, as well as to envelope proteins of the human T cell leukemia virus I and II. Previous studies have established that CKS-17 conjugated to BSA (CKS-17-BSA) inhibited IL-1-mediated tumor toxicity in melanoma cells and proliferation in murine Th clones. We examined the effects of CKS-17-BSA on IL-1 action. CKS-17-BSA did not bind to IL-1, nor did it affect the number of IL-1 receptors, their binding affinity, or their ability to internalize IL-1. However, CKS-17-BSA inhibited production of IL-2 by murine thymoma cells treated with IL-1 or with 12-O-tetradecanoyl phorbol-13 acetate. The potent protein kinase C inhibitor, H7, also inhibited IL-1-mediated responses, while HA1004, a weak inhibitor of protein kinase C, did not. Protein kinase C activity in the cytosolic fraction prepared from thymoma cells was found to be inhibited by CKS-17-BSA in a dose-dependent manner. All of these findings are consistent with the idea that CKS-17-BSA inhibits IL-1-mediated responses by interfering with signal transduction through a protein kinase C pathway.