bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the BALB/c anti-p-azophenylarsonate antibody response by monoclonal anti-idiotype. II. Idiotope expression in serum and its regulation.
Authors: Brown A R , Sealy R E 
Published: December 2022

Abstract
Five murine monoclonal antibody (mAb) anti-idiotypes (id), shown in the accompanying report by binding studies to be reactive with five different id on a single member of the 5AF6 family of BALB/c antibodies against the p-azophenylarsonate (Ar) hapten, were used to examine the distribution of their recognized id among anti-Ar in BALB/c and other mouse strains immunized with keyhole limpet hemocyanin-Ar (KLH-Ar). Differences in id expression in BALB/c and other strains substantiate that all five monoclonal anti-id reacted with different id. This suggests that the anti-id repertoire for a single antibody molecule may be extensive. Two of the anti-id reacted with id that were found in virtually all KLH-Ar immunized BALB/c mice, but constituted only a subset (approximately 33%) of the antibodies representing the 5AF6 family. The other three anti-id reacted with id infrequently expressed among BALB/c anti-Ar. Other mouse strains producing 5AF6 family anti-Ar antibodies also produced antibodies recognized by mAb 2CB8 and 6BA1; however, the three id infrequently expressed in BALB/c mice were produced in higher quantities and in a greater percent of mice. Monoclonal anti-id were capable of suppressing a portion but not all of the 5AF6 family of anti-Ar antibodies. Four of the five anti-id suppressed a greater fraction of the 5AF6 family than that id represented in a normal immune response, suggesting that suppression was mediated via an id other than that recognized by these monoclonal anti-id. Overall, the results indicate that an extensive repertoire of anti-id can be produced against a single id antibody, but suppression induced by treatment with these anti-id in this model is presumably mediated via another as yet unidentified id determinant(s).
Reactivity of E. coli-derived trans-activating protein of human T lymphotropic virus type III with sera from patients with acquired immune deficiency syndrome.
Authors: Barone A D , Silva J J , Ho D D , Gallo R C , Wong-Staal F F , Chang N T 
Published: December 2022

Abstract
Randomly sheared DNA fragments from HTLV-III proviral DNA were cloned into an E. coli open reading frame (ORF) expression vector. The inserted ORF DNA was expressed in E. coli transformants as a polypeptide fused to the lambda CI protein at the amino terminus and to beta-galactosidase at the carboxyl terminus. The reactivity of the recombinant peptides with antibodies from sera of AIDS patients was determined by the Western blot technique. The coordinates of the DNA inserts of the immunoreactive clones were then determined by DNA sequencing. A clone, ORF 628, was found to contain a short DNA segment located between the sor and env genes (nucleotide positions 5367 to 5597), a region previously thought to be noncoding. Inspection of the DNA sequences of this clone and of other HTLV-III isolates revealed the presence of a small ORF located between nucleotide position 5411 and 5625, capable of encoding a polypeptide of 72 amino acids. The biosynthesis of the polypeptide of ORF 628 initiates from an ATG codon within the HTLV-III insert. The fusion protein of ORF 628 was partially purified by affinity chromatography on CH Sepharose 4B coupled to a beta-galactosidase ligand, and tested against a panel of sera from AIDS patients by Western blot analysis. Approximately 35% of the sera from patients with AIDS or ARC contained antibodies reactive with the peptide. The DNA region spanned by ORF 628 is now thought to be the major functional element of the trans-activator gene, tat.
Anti-Ig induces release of inositol 1,4,5-trisphosphate, which mediates mobilization of intracellular Ca++ stores in B lymphocytes.
Authors: Ransom J T , Harris L K , Cambier J C 
Published: December 2022

Abstract
Evidence from a variety of laboratories indicates that crosslinking of B cell mIg induces a rapid increase in intracellular free calcium (Ca++i). This mobilized Ca++ appears to act in concert with diacylglycerol (DAG; also released upon mIg cross-linking) to optimally activate Ca++/phospholipid-dependent protein kinase C, which plays a pivotal role in B cell activation. Here we report analysis of the source of this mobilized calcium and the mechanism responsible for its release into the cytosol. We observed the cross-linking of mIg induces the release of inositol 1,4,5-trisphosphate (InsP3), presumably as a result of action of phospholipase C on plasma membrane phosphatidylinositol 4,5-bisphosphate (PtdInsP2). The release of InsP3 and the elevation of Ca++i are coincidental, suggesting that they may be causally related. Finally, we demonstrate that submicromolar doses of InsP3 induce release of Ca++ from permeabilized cells that had preaccumulated 45Ca++ in the endoplasmic reticulum. On the basis of these findings we suggest that mIg cross-linking leads to mobilization of Ca++, in part by causing hydrolysis of PtdInsP2, yielding InsP3, which in turn causes release of calcium from the endoplasmic reticulum.
Murine lymphokine-activated killer (LAK) cells: phenotypic characterization of the precursor and effector cells.
Authors: Yang J C , Mulé J J , Rosenberg S A 
Published: December 2022

Abstract
Murine and human lymphocytes incubated in recombinant interleukin 2 (RIL 2) generate a population of cytotoxic cells (lymphokine-activated killer cells [LAK]), which are able to lyse a wide array of fresh tumor cells but do not lyse fresh normal cells. Intravenous administration of these cells with the concomitant administration of RIL 2 can eliminate established pulmonary and hepatic metastases in mice. To characterize the cell that has in vitro LAK activity, we subdivided murine lymphocytes by lysing select subpopulations with the use of complement and antibodies against lymphocyte surface markers or by fluorescence-activated cell sorting. Thy-1.2-negative splenocytes were found to generate near normal amounts of LAK activity after RIL 2 incubation. Small and inconsistent LAK cell activity was generated from Thy-1.2-positive splenocytes. Ia-positive and surface immunoglobulin-positive splenocytes had little or no LAK precursor capability and did not appear to be necessary for LAK activation. Treatment of splenocytes with anti-asialo GM1 (anti-ASGM1) heterosera and complement markedly decreased their ability to generate LAK activity. At the effector stage, cytotoxic cells were of the Thy-1.2-positive, Ia-negative phenotype. Ia-depleted cells were separated into subpopulations bearing or not bearing the gamma Fc receptor (gamma FcR). The majority of cytotoxicity resided in gamma FcR-positive cells. Thus the precursors of murine LAK cells are "null" lymphocytes bearing neither T nor B cell surface markers but develop the Thy-1.2 cell surface marker in vitro, in association with the development of lytic activity for fresh tumor cells after stimulation by RIL 2.
K562 killing by K, IL 2-responsive NK, and T cells involves different effector cell post-binding trigger mechanisms.
Authors: Shanahan F , Brogan M D , Newman W , Targan S R 
Published: December 2022

Abstract
The monoclonal antibody 13.3 specifically blocks the trigger process of the NK-K562 cytolytic sequence at a post-binding effector cell level. This antibody was used to define differences in the lytic trigger processes of NK and other mechanisms of K562 lysis. Monoclonal antibody 13.3 inhibited lysis of K562 target cells by freshly isolated peripheral blood lymphocytes (PBL) and purified large granular lymphocytes (LGL), but had no inhibitory effect on antibody-dependent cell-mediated cytotoxicity to K562 by these effectors. Lectin-dependent cellular cytotoxicity (LDCC) to this target cell was also unresponsive to 13.3. The 13.3-induced inhibition of NK-K562 lytic activity persisted when PBL were activated in culture with interleukin 2 (IL 2) for periods up to 48 hr. After 48 hr of culture, the degree of inhibition diminished progressively in medium containing fetal calf serum but not in medium containing autologous serum. This 13.3-unresponsive lytic activity in cultured PBL could be attributed to more than one cell type and was present in both the LGL and Fc gamma receptor-depleted T cell fraction. Thus, K562 lysis by freshly isolated human lymphocytes via NK, K, and LDCC mechanisms is characterized by heterogeneity of the post-binding effector cell trigger mechanism. K562 lysis by lymphocytes cultured with IL 2 is similarly heterogeneous.
Mapping of SJL/J reticulum cell sarcoma tumor-associated Ia antigens by T cell hybridomas: characterization of tumor-specific and shared epitopes detected on IE+ allogeneic cells.
Authors: Ohnishi K , Bonavida B 
Published: December 2022

Abstract
Previous studies have suggested that reticulum cell sarcoma (RCS) tumor cells of SJL/J (IA + IE-) mice express neospecificities that are related to antigenic specificities characteristic of IE+ allogeneic cells. These neospecificities have also been suggested to play a role in the strong syngeneic antitumor proliferative response as well as in regulating RCS growth in vivo. The present studies characterize four RCS tumor-specific T cell hybridoma clones prepared from the fusion of BW5147 thymoma with T cells derived from lymph nodes of tumor-bearing mice. Upon stimulation, these hybridomas secrete IL 2 in the supernatant. Two hybridomas responded to RCS to IE+k and to IE+d allogeneic cells, respectively, and the other two hybridomas were tumor specific. The specificity of these hybridomas was assessed by response to both spontaneous and transplantable RCS lines and failure to stimulate a response by either normal or LPS-induced B cell blasts from the host SJL/J cells. The epitopes recognized by the T cell hybridomas were examined by the ability of several monoclonal antibodies to inhibit the IL 2-induced response by the T cell hybridomas. Antibodies directed against the IABs polypeptide of the IA hybrid molecule blocked the antitumor response by all four hybridomas. However, the response to allogeneic IE+ cells was not blocked by anti-IAs antibody but was blocked by antibodies directed against either the IAk,d or IEk,d hybrid molecules or the corresponding alpha- or beta-chains. The response to both RCS and allogeneic cells was blocked by monoclonal antibodies directed against L3T4 antigens on the T cells. Based on the exquisite specificity of the T cell receptors, the results here demonstrate that RCS tumor cells express on their surface both tumor-specific I-A-associated epitopes and Ia-associated antigenic specificities that are shared with IE+ allogeneic cells. The present studies of adapting T cell hybridomas and blocking antibodies proved useful to characterize and map distinct tumor-associated epitopes on the surface of tumor cells. These findings, when combined with structural studies, should help unravel the molecular complexity of tumor-associated antigens.
Differential association between two human MHC class I antigens and an adenoviral glycoprotein.
Authors: Severinsson L , Martens I , Peterson P A 
Published: December 2022

Abstract
The glycoprotein E19, encoded in early region 3 of adenovirus-2, forms complexes with major histocompatibility complex class I antigens. As a result of the complex formation, the intracellular transport of the class I antigens is abrogated, and adenovirus-infected cells display gradually diminishing quantities of cell surface-expressed class I molecules. To assess whether the E19 protein interacts equally well with different class I antigens, the associations between the viral protein and HLA-A2 and HLA-B7 antigens have been estimated. By infecting transfected HeLa cells expressing various amounts of HLA-A2 and HLA-B7 molecules, respectively, with various infectious doses of adenovirus-2, experimental conditions could be established that allowed quantitative estimates of the interactions to be determined. It was found that HLA-A2 molecules and the E19 protein interacts with a binding constant that is more than twice as high as that for HLA-B7 antigens and the viral protein. It is suggested that the pathogenicity of the virus may be dependent on the HLA-type of the infected individual.
Construction of human-mouse T cell hybrids that express human T cell-associated surface antigens and allow the chromosomal localization of these antigens.
Authors: van Dongen J J , Geurts van Kessel A H , Wolvers-Tettero I L , Versnel M A , van Oudenaren A , Schoenmaker E , Hagemeijer A 
Published: December 2022

Abstract
We have constructed somatic cell hybrids between the murine T cell line BW5147 and cells from patients suffering from T cell acute lymphoblastic leukemia. The obtained hybrid clones were analyzed for expression of human T cell antigens and presence of human chromosomes. T cell hybrids derived from fusion between the BW5147 cell line and bone marrow cells from a patient with pre-T acute lymphoblastic leukemia (TdT+/HLA-DR+/Tp41+/T11+/T1-/T6-/T4-/T8-/T3-) appeared to express the human T cell antigen Tp41, which can be recognized by the monoclonal antibodies 3A1 and WT1. Although this panel of hybrid cells contained all human chromosomes, no other T cell antigens were expressed. Fusion of the BW5147 cell line with peripheral blood cells from a patient with a more mature T cell acute lymphoblastic leukemia (TdT+/HLA-DR+/Tp41+/T11+/T1+/T6-/T4+/T8+/T3-) resulted in a panel of hybrid clones that expressed not only the Tp41 antigen, but also the human T cell antigens T1 and T4; two hybrids even expressed the T3 antigen. This panel of hybrids also contained the whole human genome. The two panels of human-mouse T cell hybrids allowed us to assign the genes coding for the human T cell antigens Tp41, T1, and T4 to human chromosomes 17, 11, and 12, respectively. Furthermore, these data support our previous suggestion that the expression of human lymphoid differentiation antigens in human-mouse lymphoid hybrids is influenced by the differentiation stage of the fusion partners.
Antibody-producing human-human hybridomas. III. Derivation and characterization of two antibodies with specificity for human myeloid cells.
Authors: Andreasen R B , Olsson L 
Published: December 2022

Abstract
Peripheral blood mononuclear cells from a patient with acute myeloid leukemia (AML) and spleen cells from a patient with chronic myeloid leukemia (CML) were fused with HAT-sensitive human B lymphoma cells (RH-L4) in attempts to generate human monoclonal antibodies (Mab) against antigens with high specificity for myeloid leukemia cells. Forty-seven of 246 hybridomas secreted Ig that bound to AML cell surface constituents, as determined by FACS analysis of viable cells that were FITC-stained with the human Mab as the first-step reagent and FITC-conjugated rabbit anti-human Ig as second-step. Two of the 47 human Mab (one from each patient and designated AML-19 and CML-20, respectively) bound to both autologous and allogeneic myeloid leukemia cells. No significant binding was observed to cell surface constituents on human bone marrow cells, granulocytes, lymphocytes, erythrocytes, thymocytes, monocytes, lymphoblastic leukemia cells, fibroblasts, malignant B and T lymphocytic cell lines, and murine bone marrow cells. Both human Mab were IgG and were cytotoxic to myeloid leukemia cells in the presence of complement. About 70% of peripheral blood cell samples from 46 AML patients contained AML-19- and CML-20-positive cells, but the reactivity pattern had no correlation to the morphologic FAB classification of the samples. The promyelocytic HL60 cell line and the K562 cell line reacted with the two antibodies. Dot blot analysis of binding of AML-19 and CML-20 to cellular extracts immobilized on nitrocellulose paper showed that both human Mab in this assay also reacted with normal bone marrow cells. This was supported by microscopic immunofluorescence because both human Mab stained intracytoplasmatic structures in normal bone marrow cells, but both intracytoplasmatic and cell surface components stained in myeloid leukemia cells. Moreover, immunoblotting demonstrated that both human Mab in leukemia cells reacted with two cellular proteins with Mr approximately 14,500 and 18,000, and in normal bone marrow cells with a molecule with Mr approximately 20,000. Immunoprecipitation of cell membrane molecules with both the AML-19 and CML-20 antibody precipitated from leukemic cells only the molecule with Mr approximately 18,000 and no components from normal bone marrow cells. It is concluded that myeloid leukemogenesis may result in generation of cell surface expression of either new or abnormally processed molecules that are immunogenic in the autochthonous host. These molecules may also be useful as markers in diagnosis of myeloid leukemia.
Idiotope antigens (Ab2 alpha and Ab2 beta) can induce in vitro B cell proliferation and antibody production.
Authors: Huang J H , Ward R E , Kohler H 
Published: December 2022

Abstract
We previously showed that immunization of various strains of mice with three types of antigen--PC-Hy (nominal antigen), F6-Hy (Ab2 alpha-Hy, and 4C11-Hy (Ab2 beta-Hy)--induces a differential PC-specific, T15-Id+ antibody response. In this report, the in vitro phosphorylcholine (PC)-specific B cell responses induced by these three antigens were studied. A hemocyanin-specific long-term T helper cell line was used to provide help for primary and secondary in vitro T cell-dependent B cell responses. At low doses (0.005 to 0.5 micrograms/ml) of antigen, a significant increase in the proliferation of PC-OVA-primed BALB/c B cells was observed with Ab2-Hy or PC-Hy conjugate, but not unconjugate, antigens. Similar low doses of antigen could stimulate naive B cells to secrete IgM and stimulate PC-OVA- or 4C11-Hy-primed B cells to secret IgM and IgG1 anti-PC antibodies. The percentage of T15-Id of the PC-specific antibodies produced in the in vitro T-B culture was found to be less dominant than that produced by in vivo immunization, suggesting that certain regulatory mechanisms occur in the in vivo environment that may help to maintain the T15-Id dominance. Taken together, our in vivo and in vitro results indicate that idiotope antigens can function like nominal antigens to induce antigen-specific B cell responses. The mechanisms of thymic-dependent B cell activation induced by idiotope and nominal antigen are similar in that the T-B interaction is MHC-restricted and requires cognate recognition.
Purification to homogeneity of a human hematopoietic growth factor that stimulates the growth of a murine interleukin 3-dependent cell line.
Authors: Watson J D , Crosier P S , March C J , Conlon P J , Mochizuki D Y , Gillis S , Urdal D L 
Published: December 2022

Abstract
A human lymphokine derived from the 5637 bladder carcinoma has been purified to homogeneity by using sequential reverse-phase high pressure liquid chromatography. A high recovery of biological activity is obtained by using this purification. The NH2-terminal amino acid sequence shows no homology to human interleukin 1 (IL 1), human IL 2, murine IL 3, or human granulocyte-macrophage colony-stimulating factor. The growth-promoting properties of the 5637-derived factor can be rapidly assayed by using the murine IL 3-dependent 32D c1-23 cell line. The amino acid sequence described is identical to that recently described for a human granulocyte colony-stimulating factor.
The choice between two distinct T cell determinants within a 23-amino acid region of lysozyme depends on their structural context.
Authors: Shastri N , Gammon G , Horvath S , Miller A , Sercarz E E 
Published: December 2022

Abstract
The specificity of C57BL/6 T cells reactive to peptide aa 74-96 of hen egg-white lysozyme (HEL) was analyzed by using a panel of synthetic peptides of varying lengths from this region. It was found that peptide 74-96-reactive T cells induced by native HEL (aa 1-129) or its denatured fragment L2 (aa 13-105) recognized two distinct but overlapping determinants contained within aa 74-90 or aa 81-96, respectively. Peptide 74-96 itself induced both peptide 74-90-and peptide 81-96-specific T cells. Thus, a choice was made between these two potential T cell determinants on peptide 74-96, depending on which immunogen was used. Interestingly, the ability of both peptide determinants aa 74-90 and aa 81-96 to stimulate peptide 74-96-reactive T cells was partly dependent on the presence of residues within the overlap region (aa 81-90), suggesting that this region may play an important role in Iab-restricted T cell activation. This was further supported by the poor immunogenicity of shorter peptides 74-86 or 85-96, lacking residues from the overlap region in B6 mice. These two short peptides were nevertheless capable of eliciting T cell responses in B10.A mice, suggesting that the importance of this overlap region in obtaining a response to peptide 74-96 is related to the MHC haplotype.
Only one DQ-beta restriction fragment pattern of each DR specificity is associated with insulin-dependent diabetes.
Authors: Böhme J , Carlsson B , Wallin J , Möller E , Persson B , Peterson P A , Rask L 
Published: December 2022

Abstract
Insulin-dependent diabetes is generally associated with the serologic HLA-DR specificities 3 and 4, in particular with DR-3,4 heterozygosity. The disease is negatively associated with DR-2. To investigate these associations further at the genomic level, DNA from 13 families with a proband having insulin-dependent diabetes, from 11 other individuals with the same disease, and from HLA-DR-matched control individuals was subjected to restriction fragment analysis. Three different enzymes (Bam HI, Eco RI, and Pvu II) and cDNA clones for three HLA-D region class II antigen alpha- and beta-chains (DR-beta, DQ-beta, and DQ-alpha) were used. In six families, a total of 11 siblings HLA-DR-identical to the proband were examined. There was no discrepancy between the hybridization patterns of the proband and those of the DR-identical siblings. Two different DQ-B fragment patterns were detected with each one of the serologic specificities DR-2 and DR-4. In both cases, only one of the patterns correlated significantly with diabetes. Thus, DQ-beta genomic hybridization may be used in conjunction with HLA-DR typing to identify individuals with higher relative risk to acquire insulin-dependent diabetes. These results may suggest that insulin-dependent diabetes is associated with the DQ rather than with the DR locus.