bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human T cell recognition of influenza A nucleoprotein. Specificity and genetic restriction of immunodominant T helper cell epitopes.
Authors: Brett S J , Blau J , Hughes-Jenkins C M , Rhodes J , Liew F Y , Tite J P 
Published: December 2022

Abstract
The characterization of human T cell antigenic sites on influenza A nucleoprotein (NP) is important for subunit vaccine development for either antibody boosting during infection or to stimulate T cell-mediated immunity. To identify such sites, 31 synthetic peptides that cover more than 95% of the amino acid sequence from NP of influenza A/NT/60/68 virus were tested for their ability to stimulate PBL from 42 adult donors. The most frequently recognized region was covered by a peptide corresponding to residues 206-229 of NP, with 20/42 (48%) of responders. In many individuals this was also one of the peptides that stimulated the strongest T cell responses. Other regions that were also frequently recognized were 341-362 by 13/42 (30%), 297-318 by 10/42 (23%), and 182-205 by 9/42 (21%) of individuals. These peptides covered highly conserved regions in NP of influenza A viruses, suggesting that they could be useful in boosting cross-reactive immunity against the known type A virus strains. In order to define the class II restriction molecules used to present particular T cell epitopes, 22 persons from the donor panel were HLA-typed. The majority of persons who expressed DR2, and proliferated to NP also responded to the major immunodominant region 206-229. In addition, this peptide was also immunodominant in the one person expressing DRw13. The observation that recognition of this peptide is associated with DR2 was confirmed by using short term T cell lines and APC from a panel of typed donors. Further results with virus-specific T cell lines and clones and transfected L cells expressing DR molecules showed that DR1 could also present this peptide. Therefore the results suggest that recognition of 206-229 is associated with at least three different DR haplotypes and this may explain the high frequency with which this peptide is recognized in the population. The fine specificity of the response to peptide 206-229 was distinct when presented by DR1- or DR2-expressing APC. The DR1 response was dependent on the N terminus, and the DR2 response was directed to the C terminus of the peptide.
Engagement of CD14 on human monocytes terminates T cell proliferation by delivering a negative signal to T cells.
Authors: Lue K H , Lauener R P , Winchester R J , Geha R S , Vercelli D 
Published: December 2022

Abstract
We have recently shown that engagement of the human monocytic Ag CD14 by murine mAb induces lymphocyte function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion. To determine whether CD14 plays a role in monocyte-T cell interactions, we tested the effect of anti-CD14 mAb on the proliferation of human T cells. Our results show that anti-CD14 mAb strongly inhibited T cell proliferation induced by Ag, anti-CD3 mAb, and mitogenic lectins. Inhibition by anti-CD14 mAb was epitope-dependent and required physical contact between monocytes and T cells. CD14 engagement did not affect IL-2R expression or IL-2 synthesis but induced a state of unresponsiveness that was not IL-2 specific; proliferation of anti-CD3-activated T cell blasts in response to both IL-2 and IL-4 was abrogated by addition of monocytes preincubated with anti-CD14 mAb. Inhibition of T cell proliferation after engagement of CD14 on monocytes was likely to result from delivery of a negative signal to T cells, rather than from disruption of a costimulatory monocyte-derived signal, because incubation of monocytes with anti-CD14 mAb also inhibited monocyte-independent T cell proliferation induced by PMA and ionophore. These results, together, point to a role of CD14 in the monocyte-dependent regulation of T cell proliferation.
Cross-linkage of Ly-6A/E induces Ca2+ translocation in the absence of phosphatidylinositol turnover and mediates proliferation of normal murine B lymphocytes.
Authors: Snapper C M , Yamada H , Mond J J , June C H 
Published: December 2022

Abstract
Ly-6A/E is a phosphatidylinositol (PI)-linked membrane protein whose expression is induced or upregulated on normal murine T and B cells by IFN-gamma. Cross-linkage of Ly-6A/E expressed on normal murine T cells stimulates Ca2+ translocation, and in the presence of a protein kinase C (PKC) activator, lymphokine secretion, and cellular proliferation. Utilizing an anti-Ly-6A/E mAb, we studied the effect of cross-linking Ly-6A/E on IFN-gamma-treated resting B cells, for Ca2+ translocation, PI turnover, and cellular proliferation. Since these events are known to be stimulated by cross-linkage of B cell membrane (m)Ig, we compared the changes mediated through these respective membrane proteins. We show that cross-linkage of B cell Ly-6A/E stimulates a large, rapid, and sustained increase in the concentration of intracellular free calcium ([Ca2+]i) comparable in magnitude, though somewhat delayed, relative to that observed after cross-linking of mIg. Cross-linkage of B cell Ly-6A/E does not, however, stimulate detectable PI turnover, in contrast to PI turnover induced by ligation of mIg. Both the Ly-6A/E- and mIg-mediated increase in [Ca2+]i occur through mobilization of internal Ca2+ stores as well as entry of Ca2+ into the cell from the extracellular compartment. Ly-6A/E-mediated Ca2+ translocation appears to be under the regulation of PKC in that short term pretreatment of B cells with the PKC activator, PMA, inhibits the Ly-6A/E- as well as the mIg-mediated increase in [Ca2+]i, whereas prolonged exposure to PMA, under conditions that lead to depletion of PKC, results in an augmentation in Ca2+ translocation after ligation of either Ly-6A/E or mIg. Co-capping studies indicate that Ly-6A/E and mIg cap independently in the B cell membrane, thus suggesting that the Ly-6A/E-induced effects on Ca2+ translocation are not mediated through simultaneous modulation of mIg. Anti-Ly6A/E, by itself, does not stimulate an increase in [3H]thymidine incorporation by IFN-gamma-treated resting B cells, but induces a striking increase in the presence of PMA. By contrast, anti-Ig by itself stimulates significant increases in [3H]thymidine incorporation that is inhibited by PMA. Thus, Ly-6A/E is a potent mediator of B cell activation that may use a signal transduction system in quiescent B cells that is distinct from that of the Ag receptor.
Role of Mls-1 locus and clonal deletion of T cells in susceptibility to collagen-induced arthritis in mice.
Authors: Anderson G D , Banerjee S , Luthra H S , David C S 
Published: December 2022

Abstract
The role of T cell-mediated and humoral immunity to type II collagen has been well documented in collagen-induced arthritis (CIA). Previous work from our laboratory has indicated that genomic deletions of TCR V beta genes may play a role in CIA resistance in mice. This indicated a selectivity of TCR usage by autoreactive T cells in CIA in mice. Certain strains of mice, although having a normal genomic V beta TCR repertoire, can show clonal deletion of peripheral T cells that bear specific V beta gene products in their TCR. These clonally deleted T cells are reactive with self-Ag such as minor lymphocyte stimulation (Mls) Ag. An Mls-congenic strain, BALB.D2.Mlsa, which differs only at the Mls-1 a locus from BALB/c (Mls-1b), was used to examine the effect of clonal deletion of Mls-1a-reactive T cells in CIA. These two strains were crossed to three CIA-susceptible strains, B10.RIII (H-2r, Mls-1b), DBA/1 (H-2q, Mls-1a), and B10.Q (H-2q, Mls-1b), and the crosses were injected with type II collagen. A significantly decreased incidence of arthritis was observed in the (BALB.D2.Mlsa x B10.Q)F1 hybrids, compared with (BALB/c x B10.Q)F1 hybrids, upon immunization with chick type II collagen. The BALB.D2.Mlsa cross mice also had significantly lower levels of antimouse collagen antibodies. Flow cytometric analysis confirmed the clonal deletion of Mls-1a-reactive V beta 8.1, V beta 6, V beta 7, and V beta 9 subsets in the (BALB.D2.Mlsa x B10.Q)F1 hybrids. The study of H-2q/d mice in (BALB.D2.Mlsa x B10.Q) x B10.Q back-crosses demonstrated a significant correlation between CIA resistance and Mls-1a locus. On the other hand, B10.RIII crosses showed only a modest decrease in CIA incidence in the presence of Mls-1a. As expected, all the DBA/1 crosses had an equal incidence of CIA, which was somewhat less than that seen in DBA/1 mice themselves. These studies point out that the Mls-1a locus could play a role in decreasing CIA incidence by clonal deletion of T cells bearing specific V beta TCR, which may be involved in the pathogenesis of CIA. The influence of the clonal deletion of T cells on CIA, and hence the usage of specific V beta TCR by autoreactive anti-type II collagen T cells, however, depends not only on the source of the type II collagen and the MHC class II molecules involved but also on other background genes in mice.
Suppressive effects of monocytic cells and transforming growth factor-beta on natural killer cell differentiation in autoimmune viable motheaten mutant mice.
Authors: Koo G C , Manyak C L , Dasch J , Ellingsworth L , Shultz L D 
Published: December 2022

Abstract
Viable motheaten (mev) mice are homozygous for a recessive single gene mutation at chromosome 6. These mice develop numerous inflammatory and arthritic syndromes and exhibit abnormal B cell functions as well as lower T and NK cell activity. In this study, the differentiation of NK cells in mev mice was examined to elucidate the underlying basis for decreased NK activity. Although NK cells appear to be present in mev mice, their activity was demonstrable only when the spleen cells were enriched by nylon wool passage. Similarly bone marrow cells from these mice could be shown to contain precursors of NK cells when they were passed over nylon wool and transplanted into irradiated recipients. The adherent cells from both the spleen and bone marrow of mev mice suppressed the differentiation of NK cells from normal splenic populations. These suppressive adherent cells were F4/80(+), AsGm-1(+), Qa-5(+), and NK-1.1(+). They were not cytolytic when cultured in IL-2. Antibodies to a number of cytokines, such as IFN-alpha, -beta, and gamma, or TNF-alpha, could not reverse the suppressive effect of the adherent cells. Addition of anti-TGF-beta antibody could, however, overcome the suppression, suggesting that TGF-beta was partly responsible for the defective NK differentiation in the mev mice.
Unusual alpha beta-T cells expanded in autoimmune lpr mice are probably a counterpart of normal T cells in the liver.
Authors: Seki S , Abo T , Ohteki T , Sugiura K , Kumagai K 
Published: December 2022

Abstract
Autoimmune MRL-lpr/lpr (lpr) mice develop severe lymphadenopathy, characterized by the accumulation of alpha beta-T cells with CD4-8- double negative (DN) phenotype, at the onset of disease. We previously demonstrated that the liver is a major site for the proliferation of such DN alpha beta-T cells. Herein, we further demonstrate that a large proportion of alpha beta-T cells in the liver and other organs, except the thymus, of lpr mice have unique properties, such as DN phenotype, relatively dull TCR intensity, a preponderance of V beta 8+ cells, and Pgp-1 expression. Interestingly, alpha beta-T cells in the liver of normal mice were found to consist of T cells with intermediate intensity of TCR (i.e., brighter than thymic dull TCR and lower than thymic bright TCR) as well as with bright intensity of TCR in the immunofluorescence test. These hepatic alpha beta-T cells with intermediate TCR in normal mice were found to have properties similar to those of alpha beta-T cells in lpr mice. These results suggest that abnormal alpha beta-T cells in lpr mice are a counterpart of normal T cells in the liver. An abnormal expansion of such T cells in the liver might be fundamental to the pathogenesis involved in these autoimmune mice.
Granulocyte-macrophage colony-stimulating factor promotes the proliferation of human alveolar macrophages in vitro.
Authors: Nakata K , Akagawa K S , Fukayama M , Hayashi Y , Kadokura M , Tokunaga T 
Published: December 2022

Abstract
The effects of granulocyte-macrophage (GM-CSF) or macrophage-CSF on in vitro proliferation of human alveolar macrophages (AM) were evaluated. AM of healthy volunteers incubated with recombinant human GM-CSF revealed incorporation of [3H]thymidine in vitro. The maximum incorporation was observed at 20 U/ml of GM-CSF on day 3. The proportion of proliferating cells incubated with 20 U/ml of GM-CSF from day 3 to day 4 was 8 to 11% of the total, whereas 3 to 5% of cells proliferated without GM-CSF. The number of cell nuclei increased 1.30- to 1.68-fold in the initial 7 days during incubation with 20 U/ml of GM-CSF, whereas there was a 1.07- to 1.13-fold increase without GM-CSF. Conditioned media obtained by the incubation with human lung tissue exhibited similar effects as recombinant human GM-CSF on macrophages. The effects were completely abrogated by antibody against human GM-CSF. Immunohistochemically, GM-CSF was detected in lung cells including AM, alveolar epithelium, alveolar interstitial cells, and endothelial cells. In contrast, recombinant macrophage-CSF did not induce the proliferation of human AM, although it has been known to promote the proliferation of murine AM. These observations suggest that GM-CSF plays an important role among the regulatory factors that locally support the population of AM in human lungs.
Effect of natural polymorphism at residue 86 of the HLA-DR beta chain on peptide binding.
Authors: Busch R , Hill C M , Hayball J D , Lamb J R , Rothbard J B 
Published: December 2022

Abstract
Class I and class II MHC glycoproteins are highly polymorphic molecules that bind antigenic peptides and present them on cell surfaces for recognition by T lymphocytes. Even though MHC polymorphism has long been known to affect both peptide binding and recognition by the TCR, the role of individual amino acids of MHC proteins in these interactions is poorly understood. To examine the effect of a small number of amino acid residues on T cell stimulation, B lymphoblastoid cell lines homozygous for the closely related DR1 subtypes, Dw1 and Dw20, and the DR4 subtypes, Dw4 and Dw14, were compared for their ability to present an immunogenic influenza hemagglutinin peptide (HA307-319) to an Ag-specific, DR1,4-restricted T cell clone. B cell lines expressing DR1 Dw20 and DR4 Dw14 presented HA307-319 much less efficiently than DR1 Dw1 and DR4 Dw4 and bound a biotinylated analogue of the same peptide less well. Analysis of DRB1 gene sequences suggested that polymorphism at residue 86 had a major effect on peptide binding. Differences in binding of a set of HA307-319 analogues biotinylated at each residue to cells expressing DR1 Dw1 and DR1 Dw20 suggested that the polymorphism affected the interactions of many peptide residues with the class II molecule. In inhibition assays, DR1 Dw1 and DR4 Dw4 were shown to differ from DR1 Dw20 and DR4 Dw14 in their length requirements for peptide binding. Using a larger panel of homozygous B cell lines expressing many class II haplotypes, a Ser-309 substituted HA307-319 analogue was shown to bind to most B cell lines expressing Val-86 containing alleles (including DR1 Dw20 and DR4 Dw14) but failed to bind most B cell lines expressing Gly-86 alleles (including DR1 Dw1 and DR4 Dw4). The results indicated that polymorphism at residue 86 influenced the specificity and affinity of peptide binding and affected the conformation of peptide-DR protein complexes without completely eliminating T cell recognition.
A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding.
Authors: Warmerdam P A , van de Winkel J G , Vlug A , Westerdaal N A , Capel P J 
Published: December 2022

Abstract
The low-affinity human Fc gamma RIIa is encoded by a single gene with allelic variation, defined by low-responder and high-responder alleles (LR and HR). The HR Fc gamma RIIa transcript interacts strongly with murine (m) IgG1 complexes, in contrast to the LR Fc gamma RIIa. Furthermore, the transcripts can be discriminated by mAb 41H16, which recognizes an epitope expressed on the HR Fc gamma RIIa molecule. We report that this receptor is also polymorphic in its reactivity with human (h) IgG2. Binding studies using well-defined hIgG dimers revealed that LR Fc gamma RIIa molecules can efficiently bind hIgG2, in contrast to HR Fc gamma RIIa. Previous work of others showed one amino acid difference between the allelic forms of Fc gamma RII. We, however, found a second amino acid difference between both allelic forms. In this study, hybrid Fc gamma RIIa molecules were constructed to determine the epitope for mAb 41H16 and the binding domain for mIgG1 and hIgG2 complexes. Our data point to the importance of the amino acid at position 131, located in the second Ig-like domain of Fc gamma RIIa. When an arginine residue is present at amino acid position 131, the receptor is recognized by mAb 41H16. Furthermore, the receptor can bind mIgG1-sensitized indicator E, but binds hIgG2 dimers only weakly. When a histidine residue is present at this amino acid position, hIgG2 dimers do bind efficiently to Fc gamma RII, whereas mIgG1-sensitized E and mAb 41H16 exhibit a strongly diminished binding.
Aggregated bovine IgG inhibits mannose receptor expression of murine bone marrow-derived macrophages via activation.
Authors: Schreiber S , Stenson W F , MacDermott R P , Chappel J C , Teitelbaum S L , Perkins S L 
Published: December 2022

Abstract
We previously described the presence of an inhibitory protein contained in the 20 to 40% (NH4)2SO4 precipitable fraction of FCS that down-regulates expression of mannose receptors on bone marrow-derived macrophages. We now identify aggregated bovine IgG as the main inhibitory component. Heat-aggregated bovine IgG was capable of down-regulating expression of the macrophage mannose receptor in a dose-dependent manner without inducing changes in ligand affinity whereas neither F(ab')2 fragments nor nonaggregated IgG displayed any inhibitory effect. Depleting of IgG from heat inactivated FCS by protein G affinity chromatography completely removes the inhibitory activity. Moreover, readdition of the Ig eluate from the protein G chromatography column restored inhibition in a dose-dependent manner. Macrophages were able to clear exogenously added aggregated bovine IgG, thus leading to loss of inhibitory activity in macrophage-conditioned media as compared to sham-conditioned media containing aggregated IgG. These results indicate that aggregated IgG down-regulates mannose receptor expression by macrophage activation via interaction with Fc-gamma R.
IgG subclass distribution of primary and secondary immune responses concomitant with viral infection.
Authors: Coutelier J P , van der Logt J T , Heessen F W 
Published: December 2022

Abstract
Infection with mouse hepatitis virus was found to selectively increase the proportion of IgG2a in antibodies elicited by a concomitant administration of unrelated T cell-dependent protein Ag. In contrast, T cell-independent responses were only marginally affected. This isotypic bias, which occurred when the virus was inoculated shortly before or after a primary immunization, persisted in subsequent secondary responses. However, infection concomitant to secondary antibody responses did not affect their isotypic distribution. These observations suggest that the virus can durably modify unrelated T cell responses that are initiated at the time of infection, which could have implications in the pathogenesis of autoimmune reactions.
Control of T cell responses to staphylococcal enterotoxins by stimulator cell MHC class II polymorphism.
Authors: Yagi J J , Rath S , Janeway C A 
Published: December 2022

Abstract
The bacterial toxic mitogens or superantigens are a family of related proteins that elicit potent T cell proliferative responses. These responses require APC that express MHC class II proteins, but they are not MHC restricted and they do not depend on a processing step, presumably because these mitogens bind directly to MHC class II molecules. These mitogens stimulate T cells by interacting in an unknown way with the portion of the TCR encoded by certain V beta gene segments. In this paper, we explore the importance of MHC class II polymorphism in T cell responses to staphylococcal enterotoxins. We find that certain MHC molecules present SEB to V beta 8-bearing T cells far better than others. These data suggest that one route of host defence against bacterial toxic mitogens may be to alter MHC class II molecules so that stimulation is inhibited.
CD24, a signal transducer modulating B cell activation responses, is a very short peptide with a glycosyl phosphatidylinositol membrane anchor.
Authors: Kay R , Rosten P M , Humphries R K 
Published: December 2022

Abstract
CD24 is a signal-transducing molecule on the surfaces of most human B cells that can modulate their response to activation signals by antagonizing IL-induced differentiation into antibody-forming cells and inducing proliferation in combination with signals generated by Ag receptors. A cDNA that directs the expression of CD24 on the surfaces of transfected COS cells was cloned by its homology to a cDNA encoding the murine M1/69-J11d heat stable Ag. The CD24 cDNA encodes a mature peptide of only 31 to 35 amino acids that is extensively glycosylated and is attached to the outer surface of the plasma membrane by a glycosyl phosphatidylinositol lipid anchor. Although CD24 is structurally similar to M1/69-J11d, and the two Ag appear to have a common genetic ancestry, the homology of CD24 to the M1/69-J11d Ag is confined to a small cluster of amino acids comprising potential N-linked glycosylation sites. Combined with the differences in expression patterns of the human and murine Ag, this indicates that CD24 and M1/69-J11d may not have equivalent functional roles in lymphoid development. The novel structure of CD24 suggests that signaling could be triggered by the binding of a lectin-like ligand to the carbohydrates projecting from the CD24 peptide, and transduced through the release of second messengers derived from the glycosyl phosphatidylinositol membrane anchor of CD24.
Ly-49 multigene family. New members of a superfamily of type II membrane proteins with lectin-like domains.
Authors: Wong S , Freeman J D , Kelleher C , Mager D , Takei F 
Published: December 2022

Abstract
Ly-49 (YE1/48, A1) is a dimer protein expressed on subpopulations of murine NK cells. It is a member of a superfamily of type II transmembrane proteins containing carbohydrate recognition domains (CRD). In the mouse genome, the detection of multiple restriction fragments that cross-hybridize with Ly-49 cDNA probes suggests the presence of related genes. In this study, we have isolated several genomic clones encoding portions of CRD sequences highly homologous to the CRD of Ly-49. By using primers based on the consensus sequences of the genomic clones, expression of Ly-49-related genes was detected by the polymerase chain reaction in various organs, including lung, kidney, liver, spleen, and thymus. Two full-length cDNA clones that are highly homologous to the Ly-49 gene were subsequently isolated from a lung cDNA library. At the nucleotide level, the two clones are 72% and 80% identical to Ly-49 in their translated regions, but their sequences are different from those of the genomic clones characterized to date. The two cDNA clones potentially encode type II transmembrane proteins containing CRD that are very similar to Ly-49. These amino acid sequences are also homologous to other members of the superfamily of CRD-containing type II transmembrane proteins, including hepatic lectins and the low affinity IgER (CD23). The homology is most evident in the CRD but is also significant in other domains. These results demonstrate the existence of several functional genes that are highly related to Ly-49. These genes comprise a subfamily within the superfamily of type II transmembrane proteins containing CRD.