bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular interference with antigen presentation.
Authors: Leyva-Cobian F , Unanue E R 
Published: December 2022

Abstract
Murine peritoneal macrophages were cultured with heat-killed Listeria monocytogenes organisms and then with the protein hen egg white lysozyme. Hen egg lysozyme is well known to need intracellular processing for presentation to T cells. The presentation to T cells of lysozyme was affected despite no reduction in the amount taken up or catabolized by the macrophage. This interference with Ag presentation was not found if the macrophages were cultured with lysozyme before the Listeria pulse. The interference with Ag presentation induced by Listeria was found for a second Ag (conalbumin). Uptake of Listeria did not affect the presentation of the lysozyme peptide 46-61, indicating that MHC class II molecules were available at the macrophage surface. Other materials that are retained in the macrophages affected presentation of lysozyme but not of the processed peptide. These included SRBC, dextran, sucrose, cellobiose, polyvinyl pyrrolidone, sodium dextran sulfate, Ficoll, and polyethylene glycol. Except for SRBC, which were not tested, the remaining molecules did not interfere with presentation of 46-61 by formaldehyde-fixed macrophages, an indication that they did not affect the peptide interaction with class II molecules. Finally, uptake of latex beads did not affect presentation of lysozyme. We conclude that retention in the macrophage of a variety of soluble or particulate molecules can interfere with the intracellular events that result in the creation of an immunogenic determinant. This interference is independent of the catabolism of the Ag or of the availability of class II molecules to bind peptides.
Biochemical properties of glycoproteins involved in lymphocyte recognition of high endothelial venules in man.
Authors: Jalkanen S , Jalkanen M , Bargatze R , Tammi M , Butcher E C 
Published: December 2022

Abstract
Lymphocyte interactions with high endothelial venules (HEV) are important to the in vivo migration of normal and neoplastic lymphocyte populations. We have previously described an 85- to 95-kDa lymphocyte surface glycoprotein(s) defined by mAb Hermes-1, that is involved in the recognition of HEV by human lymphocytes: antibodies against distinct epitopes of the Hermes-1 Ag differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial HEV. Here we characterize further the Hermes-1-defined glycoproteins. No well defined differences were observed between the Hermes-1 Ag immunoprecipitated from PBL and from mucosa- vs lymph HEV-specific cell lines. The Ag is an acidic (isoelectric point = 4.2) sulfated molecule bearing both O-linked and (3,4) N-linked oligosaccharide side chains. A subset of the Hermes-1-immunoprecipitated species is modified by covalent linkage to chondroitin sulfate, yielding a Mr of approximately 180 to 200 kDa. Pulse-chase labeling reveals a major precursor of 76 kDa that appears to be processed either to the 85- to 95-kDa form or, by addition of chondroitin sulfate, to a 180- to 200-kDa form. The potential role of these structural modifications, and particularly of chondroitin sulfate, in the function of the putative adhesion molecules is discussed.
Thy-1+ epidermal cells in nude mice are distinct from their counterparts in thymus-bearing mice. A study of morphology, function, and T cell receptor expression.
Authors: Nixon-Fulton J L , Kuziel W A , Santerse B , Bergstresser P R , Tucker P W , Tigelaar R E 
Published: December 2022

Abstract
We have evaluated the morphology, function, and TCR mRNA and DNA profiles of Thy-1+ epidermal cells (EC) derived from athymic (nude) mice. Based on these criteria we demonstrate that Thy-1+ EC in nude mice are predominantly round and angular and located in follicular epithelium, as compared to predominantly dendritic, interfollicular Thy-1+ EC found in normal CBA or BALB/c mice. Functionally, Thy-1+ EC from normal mice proliferate and elaborate IL-2 in response to stimulation by Con A; by contrast, nude Thy-1+ EC fail to proliferate or secrete IL-2 in response to Con A. Nude Thy-1+ EC proliferate markedly in response to low-dose IL-2 alone; Thy-1+ EC from normal mice give only modest proliferative responses to IL-2. Both populations of cells proliferate and elaborate IL-2 in response to PMA and calcium ionophore. Short-term cultured Thy-1+ EC from nude mice resemble Thy-1+ EC from normal animals in that they express no detectable functional TCR-alpha and beta-RNA. Normal Thy-1+ EC express abundant levels of functional RNA for TCR-gamma and delta-chains and for the CD3 delta-chain, whereas nude Thy-1+ EC produce no detectable TCR-delta and no CD3 delta-RNA and only truncated, presumably germ-line TCR-gamma transcripts, as suggested by lack of hybridization with gamma-V region probes and by lack of detectable rearrangements in the gamma-genes. These phenotypic, functional, and genotypic characteristics of Thy-1+ EC from nude mice suggest that these cells are at a very early stage of T cell differentiation.
The CD2 ligand LFA-3 activates T cells but depends on the expression and function of the antigen receptor.
Authors: Bockenstedt L K , Goldsmith M A , Dustin M , Olive D , Springer T A , Weiss A 
Published: December 2022

Abstract
The T cell Ag receptor (CD3/Ti) and the sheep E receptor (CD2) expressed on the surface of human T cells are both capable of initiating intracellular signals necessary for T cell activation. CD3/Ti interacts with Ag to initiate cellular immune responses. Although the exact function of CD2 is unknown, lymphocyte function-associated Ag 3 (LFA-3), a 55- to 70-kDa receptor expressed on a broad spectrum of hemopoietic and nonhemopoietic cells, has recently been shown to be its natural ligand. We show here that although purified multimeric LFA-3 is not capable of initiating transmembrane signaling events on its own, the combination of LFA-3 and the anti-CD2 mAb CD2.1 induces intracellular calcium increases, phosphatidylinositol second messenger generation and lymphokine secretion in the T cell leukemic line Jurkat. In order to study the signaling requirements of CD2, we compared the ability of CD2 mAb and LFA-3 to initiate activation signals in Jurkat and in three Jurkat-derived mutants. A CD3-CD2+ mutant failed to increase calcium or exhibit phosphatidylinositol hydrolysis to either the combination of agonist CD2 mAb 9-1 and 9.6 or LFA-3 and CD2.1. Reconstitution of the Ag receptor by transfection of the Ti-beta-chain restored the expression of the CD3/Ti complex and the ability to respond to either combination of CD2 ligands. However, no response to CD2 ligands was detected in a CD3+CD2+ mutant selected for signaling defects to CD3/Ti ligands. Complementation of the CD3/Ti signaling defect by cell fusion also restored competency to respond to CD2 agonists. These results demonstrate that LFA-3 under appropriate conditions can activate T cells via the CD2 complex and that this activation requires not only the cell surface expression of the CD3/Ti complex but also a functional Ag receptor pathway.
Triggering of co-mitogenic signals in T cell proliferation by anti-LFA-1 (CD18, CD11a), LFA-3, and CD7 monoclonal antibodies.
Authors: Carrera A C , Rincón M , Sánchez-Madrid F , López-Botet M , de Landaźuri M O 
Published: December 2022

Abstract
Proliferative T cell responses were elicited in a comitogenic assay when purified mAb against CD 18, CD11a, LFA-3, and CD7 were immobilized onto solid plastic surfaces together with submitogenic doses of mAb against the CD3 complex. The proliferative response was associated to the production of IL-2 and to the expression of IL-2R. We explored the possibility that a second signal provided by either PMA or a Ca2+ ionofore could replace the anti-CD3 mAb in the comitogenic assay. Interestingly, our data clearly indicate that PMA but not the ionofore was capable of mediating the co-mitogenic effect in conjunction with solid-bound mAb (CDw18, CD11a, LFA-3, and CD7). We also demonstrate that the mAb (anti-CD4 and anti-CD2) which have been previously described as co-mitogenic in combination with anti-CD3 are capable of eliciting this activating signal in the presence of PMA. These data indicate that mAb to certain cell surface differentiation Ag that in soluble form inhibit T cell function such as LFA-1, LFA-3, and CD2 can under appropriate conditions induce co-mitogenic signals on T cells. Our results support the hypothesis that several cell surface differentiation Ag may participate in conjunction with the T3-Ti complex in the transmembrane signal transduction leading to T cell activation.
Structure-activity studies of human IL-1 beta with mature and truncated proteins expressed in Escherichia coli.
Authors: Lillquist J S , Simon P L , Summers M , Jonak Z , Young P R 
Published: December 2022

Abstract
IL-1 beta is synthesized as an inactive 31-kDa intracellular protein, which is then processed upon secretion to an active 17-kDa carboxyl-terminal fragment. To identify the minimal portion of IL-1 beta required for activity, we constructed several deletion mutants of mature IL-1 beta. These included three amino-terminal deletions of 10, 16, and 81 amino acids, two carboxyl-terminal deletions of 17 and 72 amino acids, and one internal fragment between amino acids 17 and 81. Expression of the mutants was monitored by Western blots and immunoprecipitation. With one exception, all of these mutants and the full length 17-kDa IL-1 beta were expressed as soluble protein in Escherichia coli and could be assayed for activity and receptor binding in lysates without further purification. Whereas the intact 17-kDa IL-1 beta retained full biologic activity (greater than 10(7) U/ml of lysate) and competed for binding with 125I-labeled IL-1 beta, none of the lysates containing IL-1 beta deletion mutant proteins had activity or competed for binding to receptor at significantly higher concentrations. The loss of function in the smallest C-terminal deletion mutant does not appear to be due to the direct involvement of these C-terminal residues in receptor binding because both monoclonal and polyclonal antisera directed to this region bind to IL-1 beta but do not neutralize its activity. Therefore, this region is probably indirectly involved in sustaining the structure of the receptor-binding site.
Tumor necrosis factor-alpha affects LTR-controlled oncogene expression in transformed mouse fibroblasts at the post-transcriptional level.
Authors: Seliger B , Stark G , Pfizenmaier K 
Published: December 2022

Abstract
Potential mechanisms of TNF-alpha action on tumor cells have been investigated in a model of mouse fibroblasts transformed by distinct retroviral vectors carrying the v-mos, c-myc, and v-Ha-ras oncogene, respectively. Treatment of v-mos and c-myc transformed cells with murine rTNF-alpha in non-cytotoxic concentrations caused a strong inhibition of both proliferative capacity in monolayer culture and colony formation in soft agar. In contrast, v-Ha-ras transformed cells showed little sensitivity to TNF-alpha treatment. These changes in cell growth characteristics of v-mos and c-myc transformants was preceded by a selective reduction of oncogene-specific steady RNA levels, whereas no RNA down-regulation was observed for v-Ha-ras transformants. An unchanged transcriptional activity of the LTR-controlled v-mos and c-myc genes, but a decreased half-life of oncogene-specific mRNA suggests that TNF-alpha primarily affects stability of v-mos and c-myc RNA without influencing the activity of retroviral promoters. This is confirmed by an unchanged chloramphenicol acetyl transferase activity in TNF-treated LTR-chloramphenicol acetyl transferase transformants. Removal of TNF-alpha from cultures of reverted cells provoked a rapid retransformation, with full recovery of neoplastic growth characteristics 10 days after abrogation of TNF-alpha treatment. These data suggest that in cases of non-cytocidal action of TNF-alpha persistent suppression of tumor cell growth requires continuous TNF-alpha treatment.
Possible role of human lymphocyte receptor for IgE (CD23) or its soluble fragments in the in vitro synthesis of human IgE.
Authors: Sarfati M , Delespesse G 
Published: December 2022

Abstract
The present study demonstrates that human rIL-4 is capable of inducing the secretion of IgE by PBMC. At a concentration of 200 U/ml, an IgE response was observed in 11/26 cultures of PBMC from normal donors and in 12/15 cultures from allergic individuals. The same rIL-4-stimulated cells released significant amounts of IgE-binding factors (IgE-BF) in their culture supernatant. These IgE-BF were shown for the first time to bind simultaneously to some mAb against Fc epsilon R II (mAbER) and to soluble IgE. The lack of correlation between the rIL-4-induced secretion of IgE-BF and IgE indicates that the production of IgE-BF or the expression of Fc epsilon R II is not the only factor involved in the induction of IgE synthesis by rIL-4. However, the observation that mAbER suppressed the rIL-4-induced IgE synthesis strongly suggests that either Fc epsilon R II or IgE-BF are necessary for an IgE response. Finally, the spontaneous in vitro synthesis of IgE by enriched B cell preparations isolated from atopic donors was suppressed in an isotype-specific manner by the same mAbER or by their F(ab')2 fragments. These observations suggest that the ongoing IgE synthesis by in vivo pre-activated B cells is also regulated by IgE-BF or Fc epsilon R II. It is concluded that Fc epsilon R II or IgE-BF play an essential role both in the induction of IgE synthesis by normal B cells and in the ongoing IgE synthesis by in vivo activated B cells from allergic donors.
Avian T cells expressing gamma delta receptors localize in the splenic sinusoids and the intestinal epithelium.
Authors: Bucy R P , Chen C L , Cihak J , Lösch U , Cooper M D 
Published: December 2022

Abstract
A panel of murine mAb specific for the chicken homologues of the CD3, CD4, CD8, TCR gamma delta, and TCR alpha beta has been used to study the distribution of T cells expressing these markers in sections of chicken lymphoid tissues. These studies have revealed that the T cells possessing the two classes of TCR occupy distinct histologic microenvironments. The TCR1+ cells (gamma delta TCR homologue) are localized preferentially in the splenic sinusoids and the intestinal epithelium, where most of them express the CD8 homologue. The TCR2+ cells (alpha beta TCR homologue), a majority of which express the CD4 homologue, are found primarily in the splenic periarteriolar sheath and the lamina propria of the intestine. The frequency and distribution of the two classes of T cells in the thymus is also unique. The different tissue homing patterns of the TCR1 and TCR2 cells suggest that they represent separate lineages of T cells with distinctive physiologic roles.
IL-4 bypasses the immune suppressive effect of cyclosporin A during the in vitro induction of murine cytotoxic T lymphocytes.
Authors: Heeg K , Gillis S , Wagner H 
Published: December 2022

Abstract
We have analyzed at the clonal level the effect of IL-4 on the immune suppressive action of cyclosporin A (CsA) during the in vitro primary activation of anti-MHC alloantigen-reactive murine CD8+ CTL. Although neither IL-4 nor IL-2 alone were able to overcome the CsA-mediated suppression, the addition of IL-4 in the presence of IL-2 restored in a dose-dependent manner the induction of cytolytic activity. On the other hand, CsA greatly impaired proliferative responses of alloantigen-reactive CD8 T cells, thereby operationally dissecting proliferative responsiveness from acquisition of cytolytic activity during primary activation of alloantigen-reactive CD8+ T cells. The existence of a CsA-resistant induction pathway for Ag-specific CD8+ T cell-mediated cytolytic activity may be of relevance for experimental and clinical organ transplantation.
IgE receptor on human lymphocytes. IV. Further analysis of its structure and of the role of N-linked carbohydrates.
Authors: Letellier M , Nakajima T , Delespesse G 
Published: December 2022

Abstract
Previous studies have shown that the low affinity receptor for IgE (Fc epsilon R II) on human B lymphocytes was comprised of three components with apparent Mr of 45, 65 to 95, and 37 kDa. The present results indicate that the 37-kDa component is a soluble degradation fragment of the 45-kDa component and they also suggest that the 65- to 95-kDa component is probably made of aggregates of the above components that are formed after solubilization of the cells. The 45-kDa component appears to be a glycoprotein containing several sialic acid residues, O-linked carbohydrates and one N-linked carbohydrate chain that is of the complex type. Partial digestion of the purified 65- to 95-, 45-, and 37-kDa molecules with alpha-chymotrypsin or protease V8 generates several fragments with identical mobility on SDS-PAGE. The 37 kDa is not N-glycosylated but like the IgE-binding factors present in the culture supernatant of Fc epsilon R-bearing cells, it contains sialic acid and O-linked carbohydrates. On incubation with protease inhibitors, the Mr of IgE-binding factors (BF) is shifted from 25-27 to 37 kDa, indicating that IgE-BF are derived from the proteolytic cleavage of the 37-kDa molecule, previously identified as a membrane component of Fc epsilon R. On incubation with N-glycosylation inhibitors, the production of IgE-BF is significantly increased indicating that N-glycosylation inhibits the degradation of Fc epsilon R into IgE-BF. Inasmuch as the effect of glycosylation inhibitors is not prevented by monensin, it is concluded that all the IgE-BF are derived from surface Fc epsilon R and not from their intracellular precursors.
Identification of a surface antigen on Loa loa microfilariae the recognition of which correlates with the amicrofilaremic state in man.
Authors: Pinder M , Dupont A , Egwang T G 
Published: December 2022

Abstract
Filarial infections induce a spectrum of disease in their natural hosts, and by correlating immunity found in individuals with their disease pattern, one may delineate non-pathogenic, protective mechanisms. Loa loa is causal of mild to moderate pathology, and it is unique among the human filaria in that adult worms are occasionally visible during subconjunctival migration. To study immune mechanisms controlling microfilaremia, sera from 15 subjects with amicrofilaremic occult loiasis (OL) were compared with sera from 10 subjects with microfilaremic loiasis (ML) microfilaremia, (greater than 4000/ml) for their reactions with living microfilariae (mf). An IFA was first used to detect antibodies able to bind to the surface of living L. loa mf. ML subjects either did not react (7/10) or reacted only very weakly (3/10). Highly reactive sera were found only in OL subjects; 7/15 gave very bright fluorescence, 5/15 gave moderate reactions, and 3/15 were negative. Most of these antibodies were of the IgG class. Sera from all subjects were also reacted with living mf in an antibody-dependent cellular adherence test using normal leukocytes. Sera that were strongly positive in IFA showed strong adherence and IFA-negative sera were non-reactive. To identify the Ag involved, mf were surface iodinated, detergent-extracted Ag were immunoprecipitated, and Mr was determined on SDS-PAGE. Several OL sera, all highly reactive in the above tests, precipitated a 23-kDa molecule with which all ML sea failed to react. Sera from a mandrill experimentally infected with L. loa also precipitated the 23-kDa Ag when taken post-patency. In conclusion, it appears that certain people who control L. loa microfilaremia have high levels of IgG antibodies that bind to a surface Ag of 23 kDa and are able to mediate cellular adherence.
Effect of gamma radiation on resting B lymphocytes. II. Functional characterization of the antigen-presentation defect.
Authors: Ashwell J D , Jenkins M K , Schwartz R H 
Published: December 2022

Abstract
The effect of radiation on three discrete Ag-presentation functions in resting B cells was examined: 1) Ag uptake and processing, 2) expression of processed Ag in the context of functional class II molecules, and 3) provision of necessary co-stimulatory, or "second," signals. Analysis of radiation's effect on B cell presentation of intact vs fragmented Ag or its effect on presentation by Ag-pulsed B cells indicated that damage to Ag uptake and processing could not account for the bulk of the radiation-induced Ag-presentation defect. Experiments with phosphatidylinositol hydrolysis as an indirect measure of TCR occupancy suggested that irradiation caused a fairly rapid (within 1 to 2 h) decrease in the ability of the B cell APC to display a stimulatory combination of Ag and class II molecule. Ag dose-response analyses demonstrated that when presenting a fragment of the Ag pigeon cytochrome c to a T cell clone, 3000 rad-treated B cell APC were able to stimulate approximately 50% as much phosphatidylinositol turnover as unirradiated B cells. It was also found that, in contrast to their inability to initiate T cell proliferation, and similarly to chemically cross-linked splenocytes, heavily irradiated resting B cells plus Ag induced a state of Ag hyporesponsiveness in T cell clones. This effect on T cells had the same Ag- and MHC-specificity as did receptor occupancy required for proliferation, indicating that heavily irradiated resting B cells bear functional class II molecules. Co-culture of T cells with allogeneic B cells and syngeneic heavily irradiated B cells or chemically cross-linked splenic APC plus Ag resulted in T cell proliferation and interfered with the induction of the hyporesponsive state. This co-stimulatory function was radiosensitive in resting allogeneic B cells. Together, these data support the hypothesis that the major functional consequences of radiation to resting B cell APC are a reduction in the effective display of Ag plus class II molecules and, probably what is more important, a loss in the ability to provide APC-derived co-stimulatory signals.
BP-3 alloantigen. A cell surface glycoprotein that marks early B lineage cells and mature myeloid lineage cells in mice.
Authors: McNagny K M , Cazenave P A , Cooper M D 
Published: December 2022

Abstract
To explore the cell surface molecules expressed on pre-B cells we have produced a panel of alloantibodies against transformed pre-B cells from BALB/c mice by immunizing a wild mouse, Mus spretus. One of these antibodies, BP-3, recognized glycoproteins of Mr 38,000 to 48,000 on pre-B cells transformed either by the Abelson murine leukemia virus or an erb B oncogene construct. Removal of N-linked oligosaccharides from the BP-3 Ag revealed a single core protein of Mr 32,000. The Ag was expressed by bone marrow cells in all but one (A/J) of the inbred mouse strains tested and in wild mice of biochemical groups Mus-1 and Mus-2. Analysis of the tissue distribution revealed expression of the BP-3 reactive molecule on normal pre-B and B cells in the bone marrow, 35% of B cells in the circulation, 30% of the B cells in the spleen, and less than or equal to 20% of B cells in lymph nodes, peritoneal cavity, and Peyer's patches. The subpopulation of BP-3+ B cells in bone marrow and peripheral tissues displayed an immature phenotype (IgM IgD +/- ). Examination of a panel of transformed B lineage cells confirmed the early stage-specific expression of the BP-3 alloantigen. In addition, a myeloid cell line and normal myeloid cells were found to express the BP-3 alloantigen. In contrast to B lineage cells, the level of BP-3 expression increased as a function of myeloid cell differentiation. Myeloid cells in the bone marrow expressed relatively little Ag, whereas circulating neutrophils and peritoneal macrophages expressed relatively high levels of the BP-3 alloantigen with Mr 38,000, 41,000, and 46,000. The data suggest that this variably glycosylated cell surface protein could play different roles in the differentiation of B lineage and myeloid lineage cells. The BP-3 alloantigen appears to be a useful marker for virgin B cells that have recently migrated from the bone marrow to the periphery.