bluuebunny/crossref_metadata_2025_split huggingface dataset:
The functional significance of two amino acid polymorphisms in the antigen-presenting domain of class I MHC molecules. Molecular dissection of Kbm3.
Authors: Pullen J K , Hunt H D , Horton R M , Pease L R 
Published: December 2022

Abstract
The functional properties of two amino acid substitutions, characteristic of the bm3 mutation, in the Kb class I glycoprotein were analyzed in light of the HLA-A2 crystal model. The model predicts that amino acid residues extending into the proposed ligand-binding site or projecting up from the alpha-helices are functional with respect to peptide Ag presentation; whereas those residues pointing away from the site are silent. L cell clones expressing Kb, Kbm3, and derivatives of Kbm3, Kbm3-77 (Asp----Ser "ligand-binding") and Kbm3-89 (Lys----Ala "silent"), were generated for the analysis. Serologic characterization of this panel of cells by using the mAb B8-24-3, EH-144, 20-8-4, K9-136, and Y-25 (Kb but not Kbm3 specific) revealed the loss of the epitopes recognized by these mAb in the Kbm3-89 clone and the retention of these epitopes in the Kbm3-77 clone. Analysis of the L cell clones by using B6 anti-bm3 CTL demonstrated that L cell clones expressing Kbm3 or Kbm3-77 were lysed by these CTL, whereas clones expressing Kb, Kbm3-89, and Ld were not lysed. In reciprocal experiments, bm3 anti-B6 CTL lysed L cell clones expressing Kb or Kbm3-89 but were unable to lyse clones expressing Kbm3, Kbm3-77, and Ld. The results indicate that the substitution at amino acid 89 determines the Kbm3 serologic phenotype, whereas the Kbm3 alloreactive phenotype is primarily determined by the substitution at amino acid 77. These findings are in good agreement with the predictions derived from the x-ray crystal model of the HLA-A2 molecule.
Structures of histamine-releasing peptides formed by the action of acid proteases on mammalian albumin(s).
Authors: Carraway R E , Cochrane D E , Boucher W , Mitra S P 
Published: December 2022

Abstract
The acid proteases, pepsin, rennin and cathepsin D, were shown to generate mast cell histamine releasing peptides (HRP) when incubated with the albumin fraction of mammalian plasmas. Significant histamine release was observed using less than 1 microliter equivalent of pepsin-treated plasma. Histamine release was rapid, dependent on calcium and energy, and accompanied by degranulation. The major HRP present in pepsin-treated human and canine plasma was identified as H-Ile-Ala-Arg-Arg-His-Pro-Tyr-Phe-OH whereas that from rat plasma had valine substituted for isoleucine. Cathepsin D-treated BSA gave rise to the human octapeptide (above) as well as to an extended decapeptide with H-Tyr-Glu- at the N-terminus. These peptides were apparently derived from one region of serum albumin, residues 139 to 149 of the human, canine, or bovine sequence. We hypothesize that cathepsin D, released from leukocyte lysosomes, might generate HRP during the delayed phase of an inflammatory response.
Expression of cDNA clones encoding the thymocyte antigens CD1a, b, c demonstrates a hierarchy of exclusion in fibroblasts.
Authors: Aruffo A , Seed B 
Published: December 2022

Abstract
The CD1 gene family encodes at least three proteins: CD1a, CD1b, and CD1c, which are coexpressed on cortical thymocytes and a number of T cell leukemias. On thymocytes, CD1a forms noncovalent complexes with CD1b and CD1c, and a disulfide-linked heterodimer with CD8. This report describes the isolation and characterization of cDNA clones encoding the CD1a, CD1b, and CD1c Ag. Cotransfection of the cDNA was used to investigate the formation of intermolecular heterodimers by CD1a with other members of the CD1 gene family and with CD8. No intermolecular heterodimers were observed during transient expression in COS cells. However, an exclusion hierarchy was observed between members of the CD1 gene family when two or more members of the family were cotransfected into COS cells.
Studies on the differing effects of tumor necrosis factor and lymphotoxin on the growth of several human tumor lines.
Authors: Browning J , Ribolini A 
Published: December 2022

Abstract
The relative ability of TNF and lymphotoxin (LT) to inhibit the growth of five human tumor cell lines was examined both in the presence and absence of IFN-gamma. Two adenocarcinoma lines, HT-29 and SK-CO-1, were 20- and 320-fold more sensitive to the inhibitory effects of TNF and LT in 3- to 4-day proliferation assays. In contrast, the breast carcinoma line BT-20 showed only a one- to twofold difference. The MCF-7 and ME-180 cell lines exhibited intermediate behavior. These results parallel the reported disparate potencies of TNF and LT in their effects on endothelial cells, hematopoietic development and their abilities to sustain a mixed lymphocyte response. Radiolabeled TNF binding studies showed two classes of receptors (Kd 0.04 to 0.15 nM and 0.2 to 1.0 nM) on the highly sensitive SK-CO-1 line. HT-29 cells also appeared to possess some high affinity-binding sites, whereas the BT-20 line completely lacked the high affinity form. Thus the presence of high affinity-binding sites correlated with increased sensitivity to the antiproliferative effects of TNF. Cold TNF competed with the binding of radiolabeled human TNF three- to fivefold better than LT for binding to all three lines. These relatively small differences between the TNF and LT receptor-binding characteristics are insufficient to explain the dramatic disparity in their antiproliferative properties. Likewise, the absolute concentrations of the unlabeled cytokines necessary to block the binding of 125I-TNF were 10- to 150-fold higher than the levels necessary to elicit the biologic response. Thus, the receptor binding data conflict with the growth inhibitory effects. This discrepancy is discussed in terms of either separate receptors for TNF and LT or more complex phenomena such as receptor cooperativity possibly resulting from multivalent interactions with the trimeric form of TNF.
Analysis of antigenic domains on natural and recombinant human IFN-beta by the inhibition of biologic activities with monoclonal antibodies.
Authors: Redlich P N , Grossberg S E 
Published: December 2022

Abstract
Human IFN-beta (HuIFN-beta) is a biologically potent protein with both antiviral and antiproliferative activities. To understand better its mode of action, a number of murine mAb were developed against a recombinant (serine-17) HuIFN-beta (rHuIFN-beta ser) and screened by ELISA and neutralization of antiviral activity. The panel of antibodies, composed of both IgA and IgG immunoglobulins, were specific for HuIFN-beta and did not crossreact with HuIFN-alpha or gamma. Furthermore, three functionally distinct epitopes (designated as sites I, II, and III) were identified based on mAb neutralization of antiviral and antiproliferative activities of recombinant and natural HuIFN-beta. Antibodies directed to sites I and II neutralized the antiviral and antiproliferative activities of rHuIFN-beta ser, though the antiviral neutralization potency of the mAb to site II was approximately 10-fold less than mAb to site I. Antibodies directed to site I neutralized both recombinant and natural HuIFN-beta, although the antiviral neutralization potency was approximately 10-fold higher against rHuIFN-beta ser than the native protein. The mAb directed to site II did not demonstrate any significant neutralization of the antiviral or antiproliferative activity of natural HuIFN-beta but neutralized a recombinant HuIFN-beta containing the native sequence. Antibodies recognizing site III did not neutralize the biologic activity of either recombinant or natural HuIFN-beta. Thus, three epitopes on HuIFN-beta have been identified, two of which are associated with both antiviral and antiproliferative activities.
Modulation by antiidiotypic monoclonal antibodies of immune lysis mediated by anti-HLA monoclonal antibodies.
Authors: Ono R , Sakaguchi K , Ferrone S 
Published: December 2022

Abstract
The mAb R18-9 recognizes a cross-reacting idiotope outside the Ag-combining site of the syngeneic anti HLA-DQw3 mAb KS13, whereas the mAb R1-38, KO3-34, KO3-256, and KO3-335 recognize spatially close private idiotopes within the Ag-combining site of mAb KS13. All the analyzed Id require the association of the H and L chain of mAb KS13 for their expression. The mAb R1-38 and R18-9 were shown to markedly differ in their ability to modulate immune lysis of target cells mediated by mAb KS13. mAb R18-9 did not affect C-dependent lysis of cultured B lymphoid cells WALK mediated by mAb KS13, but enhanced cell-dependent mAb KS13-mediated lysis. mAb R1-38 inhibited both C and cell-dependent lysis mediated by mAb KS13. The effect was influenced by the incubation conditions. mAb R1-38 completely inhibited lysis when it was preincubated with mAb KS13 before being added to target cells, inhibited it partially when it was added simultaneously with mAb KS13 to target cells and did not affect it when added to target cells which had been preincubated with mAb KS13. Neither mAb R1-38 nor R18-9 in combination with mAb KS13 modulated T cell proliferation induced by allogeneic HLA mismatched lymphocytes. The system we have described may represent a useful in vitro model to investigate the mechanism(s) by which antiidiotypic antibodies may influence the outcome of organs transplanted in recipients with a history of humoral presensitization to donor's HLA Ag.
Role of IFN-gamma in lethal and nonlethal malaria in susceptible and resistant murine hosts.
Authors: Shear H L , Srinivasan R , Nolan T , Ng C 
Published: December 2022

Abstract
IFN-gamma plays an important role in host defense against microbial disease. Here, we studied the role of IFN-gamma in lethal and nonlethal murine malaria. Administration of recombinant murine IFN-gamma resulted in a dose-dependent protection of SW, BALB/cByJ, and CBA/J mice from the lethal variant of Plasmodium yoelii 17x (PyL) but had little effect on the course of the nonlethal variant of this parasite (PyNL). Administration of recombinant IFN-gamma also resulted in the activation of peritoneal macrophages for increased phagocytosis of malaria-infected erythrocytes and release of H2O2, as measured in vitro. The ability of spleen cells from infected mice to produce endogenous IFN-gamma and release H2O2 during the course of malaria was also studied. In BALB/cByJ mice, which are relatively susceptible to PyL and PyNL, there was an initial burst of IFN-gamma only in response to PyNL whereas in CBA/J mice, which are relatively resistant to these parasites, there was an initial burst of IFN-gamma in response to both PyL and PyNL. The kinetics of H2O2 release corresponded to that of IFN-gamma. In all infections, levels of IFN-gamma declined as parasitemia increased; however, nonlethal infections were characterized by a recovery of both IFN-gamma activity and H2O2 release as parasitemia declined. These data suggest that IFN-gamma may play an important role in modulating the course of malaria infections by activating macrophages for both intracellular and extracellular parasite destruction.
Autoimmune syndrome after induction of neonatal tolerance to alloantigens. CD4+ T cells from the tolerant host activate autoreactive F1 B cells.
Authors: Merino J , Schurmans S , Duchosal M A , Izui S , Lambert P H 
Published: December 2022

Abstract
The induction of transplantation tolerance to H-2b alloantigens in BALB/c (H-2d) mice by neonatal injection of (C57BL/6 x BALB/c)F1 spleen cells, produces an autoimmune lupus-like syndrome due to an activation of persisting F1 donor B cells. This syndrome is characterized by hypergammaglobulinaemia, high levels of anti-DNA antibodies, as well as by circulating immune complexes and glomerular deposits of Ig. The role of host T cells in this model was investigated by using athymic BALB/c nu/nu mice as recipients of normal (C57BL/6 x BALB.Igb)F1 spleen cells. In these "tolerized" BALB/c nu/nu mice, there was a persistence of F1 donor B cells but none of the autoimmune features were expressed, conversely to tolerized BALB/c nu/+ littermates. The injection of CD4+CD8- T lymphocytes from adult normal BALB/c mice in 3-wk-old tolerized BALB/c nu/nu mice triggered the appearance of all the autoimmune findings observed in euthymic tolerant mice. The autoantibodies were produced by persisting F1 donor B cells as shown by allotype analysis. More strikingly, a similar triggering of the autoimmune syndrome, including high titers of anti-DNA IgG antibodies and circulating immune complexes, was observed after injection of CD4+CD8- T cells from 2-wk-old tolerant BALB/c mice into "tolerized" BALB/c nu/nu mice. The anti-ssDNA antibodies were shown to bear only the Ighb allotype, indicating their exclusive origin from F1 donor B cells. These results imply that CD4+ T cells from the tolerant mice are necessary for the activation of autoreactive F1 B cells and for the development of the autoimmune syndrome occurring in this model. They also suggest that, although there is a marked depletion of H-2b-specific alloreactive CTL precursors in those neonatally tolerized mice, this state of tolerance can be associated with the persistence of H-2b-specific alloreactive CD4+ cells.
IL-6 is a potent cofactor of IL-1 in IgM synthesis and of IL-5 in IgA synthesis.
Authors: Kunimoto D Y , Nordan R P , Strober W 
Published: December 2022

Abstract
In these studies we determined the capacity of IL-6 to act as a differentiation cofactor for murine Peyer's patch B cells producing different Ig classes and subclasses. In preliminary studies we determined that sufficient endogenous IL-6 was produced in LPS-induced cell systems to obscure responses to exogenous IL-6. We therefore studied IL-6 effects on Peyer's patch B cells (T cell-depleted cell populations) in the absence of LPS, relying on responses of in vivo-activated cells. rIL-1 alpha or purified IL-6 only slightly enhanced synthesis of IgM over minimal baseline levels in Peyer's patch T cell-depleted cell cultures; however, when IL-6 was added to cultures also containing rIL-1, IgM synthesis was very substantially increased. In addition, rIL-5 alone gave rise to a modest increase in IgM synthesis and its effect was not enhanced by either rIL-1 or IL-6. IgG production (mainly IgG3) followed a similar pattern. In contrast, IgA production was only modestly increased above baseline by rIL-1, rIL-5, or IL-6 alone or by rIL-1 and IL-6 in combination, but was greatly increased by rIL-5 and IL-6 in combination. The effect of IL-6 on Ig synthesis in the above studies was not due to an effect on cell proliferation. In summary, these data indicate that B cells differ in respect to the cytokines supporting maximal terminal differentiation and thus the class of Ig produced may depend on the presence of a particular combination of cytokines and lymphokines.
Human eosinophil-derived neurotoxin and eosinophil protein X are likely the same protein.
Authors: Slifman N R , Venge P , Peterson C G , McKean D J , Gleich G J 
Published: December 2022

Abstract
The human eosinophil granule contains a series of cationic proteins. Two of these, eosinophil-derived neurotoxin (EDN) and eosinophil protein X (EPX), are reported to have similar m.w. and both possess neurotoxic and helminthotoxic activities. Therefore, the properties of these molecules were analyzed to determine whether they differ. EDN was purified from eosinophils of patients with the hypereosinophilic syndrome and EPX from the buffy coat cells of normal individuals. By SDS-PAGE, both proteins showed a major band at 18.7 kDa and a minor band at 21.4 kDa. By two-dimensional non-equilibrium gel electrophoresis the proteins migrated identically. With radiolabeled proteins in reverse phase HPLC, both proteins eluted at the same concentration of acetonitrile and showed identical tryptic maps. Both proteins possessed comparable ribonuclease activity and both were comparably neurotoxic in the rabbit. By immunodiffusion the two proteins showed a reaction of identity; by RIA, with both polyclonal and monoclonal antibodies, the proteins had very similar inhibitory activities. These results indicate that EDN and EPX have virtually identical properties and are probably the same protein.
Concerted generation of Ig isotype diversity in human fetal bone marrow.
Authors: Dosch H M , Lam P , Hui M F , Hibi T 
Published: December 2022

Abstract
The human fetal bone marrow B cell compartment of 14- to 21-wk gestational age was examined phenotypically and with respect to Ig H chain commitment and diversity. A dramatic expansion of fetal marrow B cell pools at 16- to 18-wk gestational age characterizes a rapid and concerted chain of differentiation events. Transiently up to 1/4 of nucleated marrow cells are CD20+/CD21+ cells which begin to express surface Ig other than IgM. Limiting dilution analysis of EBV-infected marrow cells delineated a virtually exclusive commitment to IgM production until 15 wk and the absolute and relative number of these cells were small (approximately 5% of comparable adult values). In parallel to the rapid increase in total B cell pools size, cells committed and able to secrete any of the five Ig isotypes are generated by 16-wk gestational age and by 18 wk the frequencies of these cells rapidly reach levels typical for adult peripheral tissue such as blood or lymph node. Fetal L chain diversity always anticipated that observed in adult serum. In addition to rising pool sizes and diverse IgH expression, EBV transformability is a major variable during this period of B cell development with up to 2/3 of B lineage cells transformable, about half of which are pre-B cells. By 21-wk gestational age transformable pre-B cells have disappeared and (as in adult tissue) approximately 10 to 20% of CD20+ cells are transformable. The rapid, concerted expression of full H chain diversity during a narrow period in fetal development is unique to marrow and implies a lymphopoietic process in a privileged site rather than an immunologic differentiation event. During this event, the relative proportions between the different IgH classes expressed, resembled that found in adult tissue, perhaps suggesting that B cell inherent programming rather than only antigenic forces determine heavy chain choice. The staggered expression, early in postnatal life, of IgH regions 3' of the C mu locus may reflect regulatory functions rather than inherent immaturity of the B lineage.
Distinct roles of IL-1 and IL-6 in human T cell activation.
Authors: Houssiau F A , Coulie P G , Van Snick J 
Published: December 2022

Abstract
We have examined the mechanisms underlying the activation of human T cells by IL-1 and IL-6. We report that PHA-stimulated accessory cell-depleted tonsillar T cells fractionated on the basis of their density show a high degree of heterogeneity in their proliferative response to these cytokines, inasmuch as small dense lymphocytes essentially fail to respond whereas large cells proliferate extensively. This differential response could be ascribed to the fact that only the large cells produced IL-2 under these circumstances, thus providing unequivocal evidence for the existence of an IL-2-mediated step in the activation of human T cells by IL-1 and IL-6. The synergy between IL-1 and IL-6 was found to result from their complementary effects on the production of and response to IL-2, with IL-1 playing a preponderant role in the induction of IL-2, and IL-6 being required, in addition to IL-1, for optimal IL-2-responsiveness. Using small tonsillar T cells, it was possible to show that, concomitant with the enhanced response to IL-2, IL-6 induced a marked increase in cell size and in protein synthesis. In the absence of other factors, this activation was not followed by entry into S phase, suggesting that the essential role of IL-6 in T cell activation is to induce the cells to move from G0 to G1, where they become more responsive to the small amounts of IL-2 induced by IL-1.
Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 bind to distinct sites on HLA-DR and HLA-DQ molecules.
Authors: Scholl P R , Diez A , Geha R S 
Published: December 2022

Abstract
Staphylococcal enterotoxins (SE) activate human T cells in vitro. This requires the presence of Ia+ accessory cells but does not require processing of the toxin by the accessory cell. We and others have recently demonstrated direct binding of SE to human MHC class II molecules. In this study, we have compared in detail the ability of class II molecules to bind two SE, toxic shock syndrome toxin-1 (TSST-1) and SEB. Scatchard analysis of equilibrium binding data indicate that SEB binds to Ia+ human cell lines with a 10-fold lower affinity than TSST-1. Likewise, SEB precipitates HLA-DR alpha- and beta-chains from detergent lysates of Ia+ cells less efficiently than TSST-1. The binding of TSST-1 and SEB to transfected L cells expressing HLA-DR and HLA-DQ gene products was differentially inhibited by anti-HLA-DR mAb. There was virtually no cross-inhibition of TSST-1 and SEB in competitive binding assays. We conclude that TSST-1 and SEB bind to two MHC class II sites which can be distinguished by their relative accessibility to blocking by anti-class II mAb and heterologous toxin.
Analysis of a monoclonal rat antibody directed to the alpha-chain variable region (V alpha 3) of the mouse T cell antigen receptor.
Authors: Utsunomiya Y , Bill J , Palmer E , Gollob K , Takagaki Y , Kanagawa O 
Published: December 2022

Abstract
Three rat mAb, RR3-15, RR3-16, and RR3-18, were established by fusing spleen cells from a rat immunized with the male Ag-specific cytolytic T cell clone, OH6, to mouse myeloma cells. The mAb was identified by their capacity to focus the cytolytic activity of the OH6 CTL clone on nonspecific target cells via FcR-FcR interaction. That all three mAb recognized the OH6 TCR was confirmed by immunoprecipitation studies in which each antibody precipitated a 90 kDa disulfide-linked heterodimer characteristic of the TCR. Surface immunofluorescence staining of a panel of T cell lines and splenic T cell populations showed that RR3-16 reacted not only to the OH6 T cell clone but also to a minor fraction of normal T cells. This reactivity was found to be due to the expression of a gene in the V alpha 3 family. However, RR3-16 did not react with all T cell lines and clones known to express genes from the V alpha 3 family. cDNA sequences of three independent RR3-16+ T cell hybridomas analyzed by polymerase chain reaction were identical to the previously published V alpha 3 sequence of the CTL clone C9. Thus, the mAb RR3-16 is specific for a single member of the TCR V alpha 3 gene family. Analysis of the expression of RR3-16+ TCR in CD4+ and CD8+ subsets of peripheral T cells demonstrated preferential expression on CD8+ T cells, suggesting regulated expression of this particular TCR V alpha gene.