bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective HLA DRA X box binding in the class II transactive transcription factor mutant 6.1.6 and in cell lines from class II immunodeficient patients.
Authors: Stimac E , Urieli-Shoval S , Kempin S , Pious D 
Published: December 2022

Abstract
6.1.6 is one of several immunoselected mutants from EBV-transformed human B cell lines that have undergone coordinate loss of expression of all their HLA class II genes. Similar defects have been found in cells from some patients with class II immunodeficiencies. Previous studies have suggested that the defects in 6.1.6 and in the other class II regulatory mutants are in transactive factors required for class II transcription. The defective factors, however, have not been identified. Here we present two lines of evidence that serve to localize the site of action of the factor that is defective in 6.1.6. First, transfected indicator genes linked to HLA DRA promoter fragments that include the conserved X box region are transiently expressed at greatly reduced levels in 6.1.6, compared with the progenitor cell line T5-1. Second, a DNA-protein complex, termed X-A, formed by nuclear extracts from T5-1 with DRA sequences containing the X box and a few bases 5' and 3' to it, is missing with extracts from 6.1.6. Extracts from some but not all patients with class II-negative immunodeficiency also fail to form X-A, whereas extracts from class II-negative mutants derived from the Burkitt's line Raji do form an apparently normal X-A complex. The X-A complex contains proteins of approximately 22, 32, 82, and 92 kDa that can be cross-linked to a 5-bromodeoxyuridine-substituted X box probe by UV light. A defect in an X box-binding protein, or in a factor required for its binding, is a likely cause for the loss of transcription of the class II genes in 6.1.6.
CD4+ T lymphocyte-induced target cell detachment. A model for T cell-mediated lytic and nonlytic inflammatory processes.
Authors: Abrams S I , Russell J H 
Published: December 2022

Abstract
We have been exploring the hypothesis that T lymphocytes have the potential to mediate immune damage through nonlytic disruption of tissue organization. In this report, we have examined the ability of purified, primary cultures of alloreactive CD4+ T cells to mediate Ag-specific target cell detachment and/or lysis of L cell lines transfected with MHC class II determinants. Using this model, we demonstrate that: 1) MHC class II-specific CD4+ T cells can cause detachment as a distinct event of the E:T interaction, although the pathways or mechanisms involved appear to be different from those utilized by MHC class I-specific CD8+ T cells; 2) detachment and lysis by CD4+ T cells are distinct activities that involve different functional requirements: 3) CD4+ T cell-induced detachment is initiated by direct cell-cell interaction, independent of TNF-alpha/beta; 4) CD4+ T cell-mediated lysis can be accomplished by TNF-alpha/beta-dependent and independent pathways; and 5) the nature of a particular target cell response to alloreactive CD4+ T cell attack reflects its intrinsic susceptibility to one or more potential effector mechanisms.
Signal transduction through class I MHC by a monoclonal antibody that detects multiple murine and human class I molecules.
Authors: Houlden B A , Widacki S M , Bluestone J A 
Published: December 2022

Abstract
We have generated a hamster anti-mouse class I reactive mAb that is capable of activating T cells in the presence of the cofactor PMA, as assayed by both IFN-gamma production and cellular proliferation. This mAb detects an epitope present on the majority of murine class I molecules, with the known exceptions of H-2Kk and H-2Kq, and is therefore not beta 2-microglobulin-specific. It also recognizes multiple human class I molecules. The epitope recognized by this antibody maps to the class I alpha 1 domain. The activation properties of this mAb are not mediated exclusively through the glycosylphosphatidylinositol-linked Qa-2 molecule, as the antibody activates spleen cells from Qa-2 negative strains. Although class I molecules are not usually considered as activation Ag, these data demonstrate their potential for involvement in signal transduction.
Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex.
Authors: Kensil C R , Patel U , Lennick M , Marciani D 
Published: December 2022

Abstract
Saponins were purified from Quillaja saponaria Molina bark by silica and reverse phase chromatography. The resulting purified saponins were tested for adjuvant activity in mice. Several distinct saponins, designated QS-7, QS-17, QS-18, and QS-21, were demonstrated to boost antibody levels by 100-fold or more when used in mouse immunizations with the Ag BSA and beef liver cytochrome b5. These purified saponins increased titers in all major IgG subclasses. To determine optimal dose in mice for adjuvant response, QS-7 and QS-21 were tested in a dose-response study in intradermal immunization with BSA in mice; for both of these purified saponins, adjuvant response (determined by stimulation of ELISA titers to BSA) neared maximum at doses of 5 micrograms and was shown to plateau up to the highest dose tested, 80 micrograms. These purified saponins vary considerably in their toxicity, as assessed by lethality in mice; the main component, QS-18, being the most toxic. Saponins QS-7 and QS-21 showed no or very low toxicity in mice, respectively. None of these saponins stimulated production of reaginic antibodies. The monosaccharide composition of these saponins showed similar but distinct compositions with all four containing fucose, xylose, galactose and glucuronic acid. Predominant differences were observed in the quantities of rhamnose, arabinose, and glucose. Monomer m.w. (determined by size exclusion HPLC) were determined to range from 1800 to 2200.
Tolerogenic ability of thymocytes in organ-cultured thymus lobes.
Authors: Matsuhashi N , Kawase Y , Suzuki G 
Published: December 2022

Abstract
It is generally believed that macrophages and dendritic cells are the major cell populations that present tolerogenic self antigens to developing thymocytes. However, it is still controversial whether self antigens expressed on thymocytes themselves work as tolerogens in the thymus. To evaluate this possibility, Thy-1 bright cells were sorted out from fetal thymus cells on the 15th gestation day, and were colonized into 2'-deoxyguanosine-treated allogeneic thymus lobes. The repopulated thymus lobes were organ-cultured, and the allo-specific killer activity of thymocytes recovered from the lobes was examined. These cells were tolerant to class I but not to class II-MHC of the donor haplotype, indicating that class I molecules expressed on the thymocytes worked as tolerogen. Tolerogenic ability of Thy-1+ cells was also demonstrated in another system. Upon intimate contact with allogeneic thymus lobes on a polycarbonate filter, thymus lobes fused with each other and Thy-1+ cells co-migrated (Eur. J. Immunol. 19:1525-1530, 1989). In thymus lobes rendered parabiotic from day 5, CTL tolerance was achieved against class I but not to class II MHC. These data indicate that thymocyte-thymocyte interaction is sufficient to induce class I CTL tolerance in developing thymocytes.
Newly identified U4/U6 snRNP-binding proteins by serum autoantibodies from a patient with systemic sclerosis.
Authors: Okano Y , Medsger T A 
Published: December 2022

Abstract
We found serum autoantibodies directed against the proteins binding exclusively to U4/U6 of Sm small nuclear ribonucleoprotein particle (snRNP) in serum from a patient (MaS) with systemic sclerosis. Their specificity, called anti-MaS, is distinct from that of known antibodies against U snRNP. The U4 and U6 small nuclear RNA from a 32P-labeled HeLa cell extract and five proteins with Mr 150,000, 120,000, 80,000, 36,000, and 34,000, in addition to Sm core proteins (B, B', D, E, F, and G) from an [35S] methionine-labeled extract, were immunoprecipitated by anti-MaS in isotonic solution. However, the Sm core proteins and U4 and U6 small nuclear RNA were separated from the protein-A-Sepharose facilitated MaS immunoprecipitate by incubation in a solution containing 500 mM NaCl. In immunoblots, anti-MaS antibodies reacted with one protein of Mr 150,000 from a HeLa cell nuclear extract that was fractionated by SDS-PAGE and transferred to a nitrocellulose sheet. The monospecific immunoaffinity purified antibody eluted from the immunoblot band immunoprecipitated U4 and U6 small nuclear RNA and reblotted the protein with Mr 150,000. These data indicate that anti-MaS antibodies recognize at least one antigenic protein that binds exclusively to the U4/U6 snRNP.
Conservation and alteration of HLA-B27-specific T cell epitopes on mouse cells. Implications for peptide-mediated alloreactivity.
Authors: Rojo S , López D , Calvo V , López de Castro J A 
Published: December 2022

Abstract
Alloreactive CTL responses generate a great variety of clonal specificities. Such diversity may be related to recognition of multiple peptides constitutively bound to any given MHC alloantigen. Among human alloreactive CTL, only a fraction of the clones lyse mouse P815 cells expressing class I HLA proteins. In this study the fine specificity of HLA-B27 allorecognition on human or mouse cells by five human HLA-B27-specific CTL clones was comparatively analyzed. This was done to examine what degree of variation in epitope structure is compatible with recognition of HLA Ag on mouse cells. Nine site-specific HLA-B27 mutants were expressed on both human and mouse cells, after DNA-mediated gene transfer, to construct two analogous series of target cells. The reaction patterns of four of the five CTL clones with these cell panels were compatible with conservation of their corresponding epitopes upon expression of HLA-B27 on mouse cells. The reaction pattern of the fifth clone was different with either cell panel, indicating that its epitope was structurally altered on mouse cells. It also suggested a selectively increased expression of the determinant on these cells. The results suggest that most of the epitopes recognized by allospecific CTL clones reacting across species are either independent of any bound peptide or involve identical peptides from both cell types. However, some of these clones recognize alloantigen-bound peptides that are somewhat different in structure depending on the cell type, and may be expressed at the mouse cell surface in greater amounts. Such peptides could arise from related proteins in both species, and be polymorphic as a result of phylogenetic divergence.
Monoclonal antibodies as probes to investigate the molecular changes of C5 associated with the different stability of the molecule on sheep erythrocytes and Escherichia coli 0111:B4.
Authors: Rottini G , Roncelli L , Narchi G , Patriarca P , Protani G , Perissutti S , Tedesco F 
Published: December 2022

Abstract
The fifth C component (C5) exhibits a different stability when bound to sheep E or Escherichia coli 0111:B4, being fairly stable on the bacterial intermediate sensitized E. coli 0111:B4 coated with C components up to C5 (BAC1-5) and extremely labile on the RBC intermediate sensitized sheep E coated with C components up to C5 (EAC1-5). We examined the possibility that molecular changes of membrane-bound C5 might be responsible for the different functional behavior of the two intermediates using mAb to C5 and sensitive immunoassays to detect bound C5. The decay of EAC1-5 over 30 min of incubation at 37 degrees C was associated with a significant drop in the reactivity of bound C5 with three of four mAb used. These results contrasted with those obtained with BAC1-5, which showed unchanged reactivity with all mAb tested over the same period of incubation. The effect of mAb on the activity of C5 was then investigated in an attempt to relate the change of the reactivity pattern of EAC1-5 with the functional modification of bound C5. MAb 1.5 and 1.6 were the only antibodies that interfered with the functional activity of C5, although through a different mechanism. In particular, mAb 1.5 was active both on fluid-phase and on membrane-bound C5 and is therefore likely to interact with the binding site for the late components on C5. Conversely, mAb 1.6 was only effective on fluid-phase C5 and acted by promoting a decay of BAC1-5 similar to the spontaneous decay of EAC1-5. We suggest that the bacterial outer membrane may protect C5 from functional decay and that mAb 1.6 interferes with the stabilizing effect of the bacteria in an as yet unclear manner.
Proposed structure of the F' allotype of human CR1. Loss of a C3b binding site may be associated with altered function.
Authors: Wong W W , Farrell S A 
Published: December 2022

Abstract
Human CR1 is composed of tandem long homologous repeating (LHR) segments that encode separate binding sites for C3b or C4b. Homologous recombination with unequal crossover has been proposed as the genetic mechanism that gave rise to the CR1 alleles that differed in their total numbers of LHR. The F allotype has four LHR, named LHR-A, -B, -C, -D, 5' to 3'. The site in LHR-A preferentially binds C4b and those in LHR-B and -C prefer C3b. A previous study revealed the presence of a fifth LHR with sequences similar to LHR-B and a third C3b binding site in the S allotype of higher m.w. In the present study, an 18-kb EcoRV fragment that was associated with the expression of the lower m.w. F' allotype hybridized with a unique pattern of cDNA and intron probes specific for LHR-C. Deletion of LHR-B and one C3b binding site was proposed as the mechanism for the appearance of this F'-specific fragment. Functional differences among the CR1 variants were sought by comparative analyses of soluble rCR1 having one, two or three C3b binding sites. Although these three variants did not exhibit any significant differences in their capacities to act as cofactors for the cleavage of monomeric C3b, their relative affinities for dimeric ligand varied more than 100-fold. Furthermore, the variant with only one C3b binding site was at least 10-fold less effective in the inhibition of the alternative pathway C3 and C5 convertases. These observations suggested that the F' allotype may be impaired in its capacity to bind opsonized immune complexes, to inhibit the formation of the alternative pathway C3 and C5 convertases, and perhaps to mediate other CR1-dependent cellular responses.
Signal transduction events and Fc gamma R engagement in human neutrophils stimulated with immune complexes.
Authors: Walker B A , Hagenlocker B E , Stubbs E B , Sandborg R R , Agranoff B W , Ward P A 
Published: December 2022

Abstract
Signal transduction events have been evaluated in human neutrophils stimulated with immune complexes consisting of polyclonal rabbit antibody complexed with BSA. Immune complexes induced dose-related O2- responses, but very small increases in intracellular calcium ([Ca2+]i) levels were observed, in contrast to FMLP-stimulated cells. Measurements employing [45Ca2+] demonstrated that calcium influx and efflux in cells stimulated with immune complexes was substantially less than fluxes found in FMLP-stimulated cells. With respect to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) formation under conditions in which the O2- responses to immune complexes or FMLP were similar, the Ins(1,4,5)P3 response to immune complexes was much smaller (by 65%) as compared to that induced by FMLP. Although pertussis toxin-treated cells showed a greatly diminished O2- response (by 89%) to FMLP, the response to immune complexes was largely resistant (only 26% reduction) to the inhibitory effects of this toxin. Antibodies to Fc gamma R indicated that engagement of Fc gamma RII and Fc gamma RIII, but not Fc gamma RI, receptors was related to the O2- response of neutrophils to immune complexes. O2- formation occurred in neutrophils incubated with Staphylococcus aureus cell walls bearing antibodies to Fc gamma RII or Fc gamma RIII. These data indicate that, in human neutrophils stimulated with immune complexes, signal transduction events involve engagement of Fc gamma RII and Fc gamma RIII. The O2- response is largely pertussis-toxin insensitive, is not associated with a significant increase in levels of [Ca2+]i, and is associated with relatively little formation of Ins(1,4,5)P3. This is in contrast to cells stimulated with FMLP in which O2- responses are largely pertussis toxin-sensitive and associated with large increases in [Ca2+]i as well as formation of Ins(1,4,5)P3. Signal transduction events involving Fc gamma R appear to be quite different from those events related to engagement of FMLP receptors.
A T cell epitope in VP1 of foot-and-mouth disease virus is immunodominant for vaccinated cattle.
Authors: Collen T , Dimarchi R , Doel T R 
Published: December 2022

Abstract
Synthetic peptides representing regions of the VP1 protein of foot-and-mouth disease virus strain 01 Kaufbeuren were screened for their ability to stimulate proliferation of PBMC from virus vaccinated cattle. Sites were identified at residue 21-40 (peptide FMDV32) and in the region C-terminal to residue 161. Cells responding to FMDV32 were MHC class II-restricted, CD4+ and secreted IL-2. Thus, this region is defined as a Th site. Of 19 virus vaccinated Friesian cattle, 89% (17/19) responded to purified virus while 37% (7/19; 41% of virus responders) also responded to FMDV32 suggesting that this site is immunodominant for the cattle used. Furthermore, immunisation of FMDV32 responder and non-responder cattle with a related peptide, FMDV5 (FMDV32 co-linearly synthesized with the 141-160 VP1 B cell site), induced neutralizing antibody and a virus-specific T cell population in the FMDV32-responder but not the non-responder animals.
Heavy chain variable region gene families evolved early in phylogeny. Ig complexity in fish.
Authors: Ghaffari S H , Lobb C J 
Published: December 2022

Abstract
The V regions of channel catfish H chain cDNA clones have been analyzed. Based upon sequence relationships and hybridization analyses, five different groups of VH genes are identified whose definition is consistent with that of five different VH families. Genomic Southern blots indicate that as many as 100 different germ-line VH genes are likely represented by these families. The sequence diversity between identified members of these different families is similar in magnitude to the divergence represented between members of different human or mouse VH families. The FR regions are the most conserved regions when members of different catfish VH families are compared; specific amino acid positions appear to be highly conserved in phylogeny. Equally important is that diversity is represented in complementarity-determining regions CDR1 and CDR2 in members of the different families as well as in members of the same VH family. These results suggest that an extensive repertoire of VH genes can contribute to antibody diversity in this lower vertebrate. Sequence comparisons indicate that one of the catfish VH families shares considerable structural similarity to several higher vertebrate VH gene families--a relationship which suggests that this VH family may be ancestral to some VH gene families of higher vertebrates. Characteristic of the genomic organization of higher vertebrate H chains, catfish appear to have different VH families wherein a VH gene likely undergoes functional recombination with putative DH gene segments and one of apparently several different JH segments. The recombined V region is expressed with the same C region gene. These combined results suggest that bony fishes are the earliest known phylogenetic representatives to have evolved extensive V region gene families.
Identification of encephalitogenic V beta-4-bearing T cells in SJL mice. Further evidence for the V region disease hypothesis?
Authors: Padula S J , Lingenheld E G , Stabach P R , Chou C H , Kono D H , Clark R B 
Published: December 2022

Abstract
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system mediated by T cells bearing TCR of restricted heterogeneity. Thus, in the murine PL strain, V beta-8.2 is used by 80% of the encephalitogenic T cells. This observation has led to the successful prevention and reversal of EAE by the in vivo use of mAb directed to these restricted gene products. In SJL mice, the V beta-17a gene product has been shown to be used by approximately 50% of encephalitogenic T cells subsequent to immunization with a myelin basic protein (MBP)-derived peptide. However, the other V beta genes used by encephalitogenic T cells in SJL EAE have remained uncharacterized. We now report, for the first time, the beta-chain-encoding DNA sequence of two encephalitogenic, MBP-reactive, SJL-derived T cell clones. These clones which are specific for H-2s and the carboxyl-terminus (amino acid 92-103) of MBP, use TCR encoded by V beta-4. In addition, we demonstrate that the transfer of EAE by a heterogenous SJL-derived encephalitogenic T cell line can be prevented using an anti-V beta-4 antibody in vivo. V beta-4 usage has been previously described in a H-2u/MBP amino-terminus-reactive encephalitogenic T cell. The present findings may thus further support the "V region-disease" hypothesis.
Synergistic action of monoclonal antibodies directed at p55 and p75 chains of the human IL-2-receptor.
Authors: Audrain M , Boeffard F , Soulillou J P , Jacques Y 
Published: December 2022

Abstract
TU27, a mouse IgG1 mAb directed at the p75 chain of the human IL-2R, was analyzed for its ability to interact with IL-2 binding on isolated p75 chains (YT-2C2 cells) and high affinity p55/p75 receptors (human alloreactive T cell clone 4AS), to inhibit IL-2-induced proliferation (4AS cells) and to cooperate with an anti-p55 chain mAb (33B3.1) for inhibiting IL-2 binding and proliferation. TU27 and IL-2 bound to the isolated p75 chain expressed by YT-2C2 cells with respective dissociation constants (Kd) of 1.3 and 1 nM. They cross-inhibited each other for binding with inhibition constants (Ki) in agreement with their respective Kd values. The nature of the interaction was, however, not purely competitive and suggested nonidentical epitopes for the two ligands on the p75 chain. On 4AS cells, IL-2 bound with high affinity (Kd = 50 pM) and TU27 with an affinity similar to that found on YT-2C2 cells. The binding of TU27 and IL-2 were also mutually exclusive on 4AS cells. However, the mechanism of interaction of TU27 with IL-2 was complex since the inhibitory potency of the antibody depended on temperature, antibody preincubation and time of assay. Data obtained at 4 degrees C in the presence of suboptimal, tracer-like concentrations of IL-2 indicated that the intrinsic affinity of TU27 for the high affinity configuration was 15-fold lower than for the isolated p75 chain and argued in favor of the affinity-conversion model (as opposed to the preformed complex model) in which p55 and p75 are dissociated in the absence of IL-2. At 37 degrees C, TU27 inhibited IL-2 binding only on short time assays (6 min). Longer time (30 min) of IL-2 binding resulted in an almost complete disappearance of the effect of TU27, suggesting that internalization of the high affinity p55/p75/IL2 complex enables the cells to escape from the inhibitory effect of TU27. In the presence of the 33B3.1 mAb, the interaction of TU27 with IL-2 resembled the one observed on YT-2C2 cells, suggesting that 33B3.1 is able to inhibit the IL-2-induced association of p55 and p75. Both antibody were found to synergize on 4AS cells, as a result of a cooperative mechanism in which 33B3.1 blocks the formation of the high affinity complex hence allowing TU27 to bind with higher affinity, and TU27 blocks IL-2 binding to the p75 chain. Proliferation studies corroborated the binding experiments.(ABSTRACT TRUNCATED AT 400 WORDS)