bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell recognition of fibrinogen. A determinant on the A alpha-chain does not require processing.
Authors: Lee P , Matsueda G R , Allen P M 
Published: December 2022

Abstract
Murine T cell hybridomas were used to examine the requirements for processing and presentation of human fibrinogen. In contrast to most protein Ag, fibrinogen (Mr 340,000) did not need to be processed by an APC, inasmuch as intact fibrinogen was presented by both pre-fixed and chloroquine-treated macrophages. Through the use of a variety of protease inhibitors, no involvement of proteases either on the macrophage surface or in the culture medium in the presentation of fibrinogen was observed. The epitope recognized by two T cell hybridomas was localized to the peptide, A alpha (551-578), which was located on the carboxy portion of the A alpha-chain. This portion of the A alpha-chain has no defined secondary structure and must possess the conformational flexibility which allows it to directly associate with an I-Ek molecule. Thus conformational flexibility may be a major factor in determining the processing requirements of a protein Ag.
Processing by accessory cells for presentation to murine T cells of apamin, a disulfide-bonded 18 amino acid peptide.
Authors: Régnier-Vigouroux A , el Ayeb M , Defendini M L , Granier C , Pierres M 
Published: December 2022

Abstract
Apamin, an 18 amino acid peptide with two disulfide bonds, elicits specific T cell proliferative responses in H-2d and H-2b mouse strains. We evaluated the processing requirement of this compact peptide by accessory cells for presentation to apamin-reactive T hybridoma cells (THC) by analyzing the IL-2 responses of 16 THC from apamin-primed BALB/c or C57BL/6 mice, to various forms of either native or chemically synthesized apamin analogs. These included: unfolded peptides (whose four sulfhydryl groups were blocked by acetamidomethyl residues), N-and/or C-truncated peptides, and an analog with a single amino acid substitution at position 10. Assessment of the Ag-specific THC responses in the presence of either live or formaldehyde-prefixed APC indicated the following: 1) all THC stringently required Ag processing; 2) in 8 of 16 cases, the simple unfolding of apamin was sufficient to eliminate the need for Ag processing, or even induced increased THC IL-2 responses (other cells required further antigenic alterations in addition to unfolding, or rare processing steps dependent on the integrity of the two disulfide bonds); and 3) for most THC, the Leu10 and the N terminus arm of apamin were shown to be critical for expression of the epitopes involved in T cell recognition. These data indicate that apamin, a natural peptide having an appropriate size for T cell triggering, acquires its antigenic conformation after a processing by APC which primarily involves an alteration of a disulfide bond-dependent peptide folding.
The biologic activity of anti-T cell receptor V region monoclonal antibodies is determined by the epitope recognized.
Authors: Rojo J M , Janeway C A 
Published: December 2022

Abstract
We have used 10 independently isolated mAb reactive with the Ag R on a cloned Th cell line to map three distinct epitopes and three subepitopes on the R. One of these epitopes is clearly on the V beta 8 region, as it is defined by the antibodies KJ-16 and F23.1, known to react with the V beta 8 family of variable regions, and a functional rearranged V beta 8 gene has been cloned from this cell line. Antibodies directed at a second epitope, believed to be on V alpha because it is unaffected by anti-V beta antibodies, are completely inhibited from binding by monoclonal anti-CD3 epsilon-chain antibodies. Because the cloned Th cell line used, D10.G4.1, responds to soluble monoclonal anti-TCR antibodies, it has been possible to compare the binding of anti-R antibodies with their ability to activate this cloned T cell line. We find that for antibodies all specific for the same or a closely related epitope, activation is proportional to binding, by using antibodies that differ by greater than 100-fold in avidity for the R. By contrast, antibodies directed at different epitopes on the R differ markedly in their ability to activate the D10.G4.1 cell line. We have tested whether these differences reflect differences in the orientation of cross-linking the TCR or possible conformational changes induced in the R by the antibodies, and our data support the latter hypothesis as an explanation for the differences in activation potency between antibodies.
B cell stimulatory factor 1 (IL-4) enhances the development of cytotoxic T cells from Lyt-2+ resting murine T lymphocytes.
Authors: Trenn G , Takayama H , Hu-Li J , Paul W E , Sitkovsky M V 
Published: December 2022

Abstract
B cell stimulatory factor 1 (BSF-1) (IL-4) was shown to synergize with phorbol esters or with monoclonal anti-TCR antibody in stimulation of the development of CTL from small resting murine T cells. IL-2 also synergized with PMA in such differentiation but was less effective than BSF-1. The combination of these two lymphokines with PMA had the most potent effect on the development of CTL. BSF-1 plus PMA stimulated a significant increase in the intracellular content of N-benzyloxycarbonyl-L-lysine thiobenzylester esterase, a granule-associated biochemical marker, whereas IL-2 plus PMA was only marginally effective. Depletion of L3T4+ cells did not result in the abrogation of these effects. Lyt-2+ T cells that were incubated for 72 h with BSF-1 plus PMA accumulated N-benzyloxycarbonyl-L-lysine thiobenzylester esterase and secreted this intragranular marker after interaction with immobilized anti-T cell receptor mAb. These BSF-1/PMA-stimulated Lyt-2+, L3T4- T cells were also able to kill FcR positive target cells in a retargeting assay with a mAb to murine T3 Ag, providing evidence that BSF-1 plus PMA acted directly on precursors of cytotoxic T cells.
Soluble IL-2 receptor levels in serum from blood donors seropositive for HIV.
Authors: Prince H E , Kleinman S , Williams A E 
Published: December 2022

Abstract
Serum levels of soluble IL-2R (sIL-2R) were measured in blood donors seropositive for HIV. Approximately one-half (53/101) of these seropositive donors exhibited increased serum sIL-2R levels compared with seronegative controls (n = 65). Further, a significant inverse correlation was observed between serum sIL-2R levels and CD4 cell levels in seropositive study participants. These findings suggest that increased serum sIL-2R levels in HIV infection may be linked to CD4 cell loss, and thus reflective of the stage of HIV-induced disease.
Plasma membrane-associated tumor necrosis factor. A non-integral membrane protein possibly bound to its own receptor.
Authors: Bakouche O , Ichinose Y , Heicappell R , Fidler I J , Lachman L B 
Published: December 2022

Abstract
Purified plasma membranes from LPS-activated human blood monocytes produced significant lysis and growth inhibition of the TNF-sensitive L929 murine fibroblast cell line. Unactivated human monocyte plasma membranes did not display either activity. Anti-TNF serum specifically inhibited the anti-tumor activity of activated monocyte membranes whereas anti-IL-1 serum or non-specific rabbit serum decreased neither the lysis nor growth inhibition of L929 cells. Membrane-associated TNF did not behave as an integral protein as it could be eluted from the plasma membranes by either high salt or low pH treatment. Plasma membranes cleared of membrane-associated TNF by high salt treatment were able to bind TNF, and this binding was specifically inhibited by preincubation of rTNF with specific anti-TNF serum. Western blot analysis of plasma membranes showed a membrane-associated TNF with a m. w. of approximately 17 kDa present only in the activated monocytes. When the plasma membranes were preincubated with the cross-linker agent dissuccinimidyl suberate, Western blot analysis revealed the presence of a TNF-binding protein with a Mr of approximately 102 kDa. These studies indicate that unlike IL-1, membrane-associated TNF is not an integral membrane protein and that TNF may be associated with the monocyte membrane by occupying the TNF R.
Production of two hemopoietic growth factors is differentially regulated in single T lymphocytes activated with an anti-T cell receptor antibody.
Authors: Kelso A , Owens T 
Published: December 2022

Abstract
A method has been developed to measure the production by single activated T lymphocytes of two hemopoietic growth factors, granulocyte-macrophage CSF (GM-CSF) and multipotential CSF (multi-CSF or IL-3). When individual cells of the L3T4 (CD4)+ F23.1+ T cell clone E9.D4 were transferred by micromanipulation into wells coated with the monoclonal anti-T cell receptor antibody F23.1, up to 90% of cells produced CSF as detected by CSF-dependent hemopoietic cell lines. Production occurred in the absence of proliferation and did not require the addition of accessory cells or IL-2. Both the frequency of CSF-producing cells and the average production per positive cell depended on the density of the immobilized stimulating ligand, indicating that the response of each cell is not an all-or-none phenomenon but varies with the strength of stimulation. Individual cells of the clone varied over a 100-fold range in their total CSF titer with a mean value of about 0.05 U/cell. They also varied in their relative production of GM-CSF and multi-CSF. Thus, low producing cells secreted only GM-CSF whereas high producing cells also secreted multi-CSF. The failure of low producing cells to secrete multi-CSF was not genetically based since such cells could give rise to progeny that synthesized multi-CSF. These results suggest that the synthesis of these two lymphokines can be differentially regulated at the level of the single cell.
Characterization of prion proteins with monospecific antisera to synthetic peptides.
Authors: Barry R A , Vincent M T , Kent S B , Hood L E , Prusiner S B 
Published: December 2022

Abstract
The prion protein (PrP) 27-30 is the major macromolecular component in highly purified preparations of prions derived from scrapie-infected hamster brain. Immunoblotting studies demonstrated that this protein is generated by partial protease digestion of a larger precursor (PrPSc) with an apparent Mr of 33 to 35 kDa, and that a protease-sensitive cellular PrP isoform, designated PrPC, is present in normal hamster brain. To characterize the relationships among these proteins, ELISA and immunoblotting studies were undertaken with rabbit antisera raised against three synthetic PrP peptides. All three antisera were found to specifically react with the prion proteins, and failed to identify other lower or higher m.w. PrP proteins. Our results provide evidence that the primary structures of PrP 27-30, PrPSc, and PrPC are related; this conclusion supports molecular cloning studies indicating that these proteins are encoded by the same chromosomal gene.
A novel guinea pig macrophage-specific polymorphic molecule. I. Biochemistry, genetics, and tissue distribution.
Authors: Jensen L A , Schwartz B D 
Published: December 2022

Abstract
In the course of studying Ia molecules from strain 2 and strain 13 guinea pig macrophages, with the intent of comparing them to B cell Ia molecules, it was observed that guinea pig alloserum prepared by cross-immunization of guinea pig lymphocyte Ag non-identical inbred guinea pigs immunoprecipitated not only conventional class I and class II molecules, but also a 98,000-Da molecule, termed gp98. Two different forms of the molecule were detected, indicating it is polymorphic. The genes encoding gp98 were shown not to be linked to the guinea pig lymphocyte Ag complex. The molecule gp98 was found on macrophages within populations of peritoneal exudate cells, resident peritoneal cells, bone marrow cells, and spleen. All gp98-bearing macrophages were also Ia-positive. However, only a subpopulation of macrophages bore gp98. The gp98 was not found on Ly-1 or Ig-bearing cells, indicating that B and T cells do not bear Ia. Thus, gp98 appears to be a highly immunogenic polymorphic macrophage-specific molecule that allows the characterization of guinea pig macrophage subsets.
HA2 subunit of influenza A H1 and H2 subtype viruses induces a protective cross-reactive cytotoxic T lymphocyte response.
Authors: Kuwano K , Scott M , Young J F , Ennis F A 
Published: December 2022

Abstract
Influenza H1 subtype-specific CTL can be induced by secondary stimulation of a hybrid protein of the first 81 amino acids of the viral NS1 non-structural protein and the HA2 subunit of A/Puerto Rico/8/34(H1N1) hemagglutinin. In addition, a derivative of this protein with 65 amino acids deleted from the N-terminal end of HA2 can also generate H1 subtype-specific CTL in bulk cultures. CTL clones established by stimulation with the derivative protein demonstrated cross-reactive lysis of target cells infected with virus strains of the H1 and H2 subtypes. Cold target competition experiments with CTL clones as effectors demonstrated that the Ag specificity between these two hybrid proteins is identical. Adoptive transfer of the CTL clone significantly reduced virus titers in the lungs of mice infected with the virus strains of the H1 or H2 subtype but not those infected with the H3 subtype virus in vivo, which reflects the in vitro CTL clone activity. These experiments demonstrate that an epitope on the hemagglutinin that is conserved on virus strains of the H1 and H2 subtypes induces a protective CTL response. These results suggest an alternative approach for developing influenza vaccines by using conserved antigenic sites on the hemagglutinin HA2 subunit to avoid the problem of frequent antigenic mutations of the HA1 subunit antibody binding sites.
Effective immunization against cutaneous leishmaniasis with defined membrane antigens reconstituted into liposomes.
Authors: Russell D G , Alexander J 
Published: December 2022

Abstract
The abundant Leishmania promastigote surface Ag gp63 and Leishmania promastigote lipophosphoglycan were reconstituted into liposomes and used as a vaccine against the agent of New World cutaneous leishmaniasis, Leishmania mexicana. The Ag were inoculated s.c., i.p., and i.v. into CBA/ca and BALB/c mice. Even at low Ag dosages, 8 to 10 micrograms/mouse, the Ag induced appreciable levels of protection. In CBA/ca mice complete protection was obtained by s.c. inoculation of antigen-containing liposomes. Protection could be transferred with T cells to naive mice. Interestingly, the Ag-containing liposomes did not cause the disease exacerbation observed in previous vaccine studies with crude parasite extracts.
Virus-lymphocyte interactions. II. Expression of viral sequences during the course of persistent lymphocytic choriomeningitis virus infection and their localization to the L3T4 lymphocyte subset.
Authors: Tishon A , Southern P J , Oldstone M B 
Published: December 2022

Abstract
Viruses that cause in vivo persistent infections need to selectively compromise the host's immunologic surveillance machinery in order to survive. To understand the molecular basis of how this is accomplished we have analyzed persistent virus infection by lymphocytic choriomeningitis in its normal host, the mouse. Earlier we noted by infectious center analysis that five in 10(4) lymphocytes carried by persistently infected mice contained infectious materials throughout the course of infection. A previous publication extended these results, in BALB mice by showing that the L3T4+ lymphocyte subset in lymph nodes and spleens was predominantly involved. Using cDNA labeled probes to the viral genome and in situ hybridization we report that 1 to 2% of circulating lymphocytes from several mouse strains contain viral RNA sequences for the three viral structural genes. By FACS analysis, the Thy-1.2+, L3T4+ subset primarily harbors virus while viral sequences are usually not detected in the Lyt-2+ subset as early as 6 days after initiating infection in newborns and throughout the course of the persistence. These findings suggest that incomplete, presumably defective, virus is generated in a subset of Th lymphocytes during persistent infection and that during this time infection of cytotoxic T cell subsets is minimal.
Monoclonal antibody against IFN-gamma inhibits Moloney murine sarcoma virus-specific cytotoxic T lymphocyte differentiation.
Authors: Zanovello P , Vallerani E , Biasi G , Landolfo S , Collavo D 
Published: December 2022

Abstract
The role of autochthonous IFN- production was evaluated in immune reactions to Moloney murine sarcoma virus (M-MSV)-induced tumors which are characterized by spontaneous regression mainly caused by virus-specific CTL activity. A functional IFN- depletion, induced by repeated administration of mAb anti-IFN- at the site of virus inoculation, prevented tumor regression in M-MSV-injected mice. Moreover, this antibody inhibited in vitro both proliferation and differentiation of M-MSV-specific T lymphocytes obtained in bulk cultures, but not growth and lytic activity of the already differentiated virus-specific CTL clone CHM-14 stimulated with rIL-2 and relevant tumor Ag. In addition, in mice receiving mAb treatment the frequency of M-MSV-specific CTL precursors, evaluated by means of limiting dilution analysis, was strongly reduced in comparison with that of control mice injected only with virus. Because CTL secrete IFN- following antigenic stimulation, the possibility that non-T effector cells recruited by this lymphokine might mediate tumor regression was also considered. Adoptive immunotherapy experiments, performed in T cell-deficient (Tx + BM) and in sublethally irradiated mice, demonstrated that transfer of CHM-14 CTL clone, which secretes IFN-, was able to counteract M-MSV tumor growth despite the local mAb anti-IFN- treatment which may have prevented host cell recruitment. Moreover, repeated local rIFN- inoculations in Tx + BM mice did not counteract M-MSV tumor progression, thus confirming that other IFN- properties such as non-T cell recruitment, antiviral or anti-proliferative IFN- activities have little or no relevance when M-MSV-specific CTL are lacking. On the whole, these results indicate that in M-MSV-injected mice, tumor enhancement after mAb anti-IFN- treatment is principally caused by impaired differentiation of virus-specific CTL precursors.
Loss of CD45R (Lp220) represents a post-thymic T cell differentiation event.
Authors: Serra H M , Krowka J F , Ledbetter J A , Pilarski L M 
Published: December 2022

Abstract
CD45R+ and CDw29+ CD4+ T cells are widely regarded as separate functionally defined T cell lineages. The work described here indicates that they represent maturation stages within the same differentiation pathway. Purified populations of CD4+ or CD8+ T cells, after stimulation with PHA, lose cell surface expression of CD45R (Lp220) and gain an increased surface density of CDw29 (4B4). Clonal analysis demonstrated that individual CD4+ CD45R+ T cells lost CD45R and acquired CDw29 with time in culture. This effect was selective for the high Mr 220-kDa form of the T200 (CD45) complex because the density of CD45, detected by an antibody to common determinants, did not decrease. This strongly indicates that CD45R+ cells are an immature stage in a lineage that culminates in CDw29 expression. To further define the expression of CD45R and CDw29, we analyzed infant thymus cells. Thymocytes include only 4 to 6% CD45R+ cells, but 95% express CDw29 in moderate density. The CD45R+ set appears to include mainly single CD4+ or CD8+, CD3 "bright" medullary cells, although only 15 to 25% of thymocytes with medullary phenotype express CD45R. In vitro culture of thymocytes with Con A and T cell growth factor induces expression of CD45R but these cells differ from the peripheral CD45R+ set by virtue of their co-expression of a high density of CDw29 (4B4) Ag. We postulate that post-thymically CD45R (Lp200) and CDw29 (4B4) comprise a functional assembly on the surface of T cells that changes in composition after stimulation with Ag or mitogen. This may result in enhanced ability of an Ag-experienced T cell to respond effectively to Ag due perhaps to a more efficient signaling complex.
Subpopulations of early thymocytes. A cross-correlation flow cytometric analysis of adult mouse Ly-2-L3T4-(CD8-CD4-) thymocytes using eight different surface markers.
Authors: Wilson A , D'Amico A , Ewing T , Scollay R , Shortman K 
Published: December 2022

Abstract
Putative early thymocytes, the Ly-2-L3T4-(CD8-CD4-) cells representing 3 to 4% of adult CBA mouse thymic lymphocytes, were isolated in high purity (99.5%). They were then stained by using mAb and analyzed by flow cytometry for the expression of six additional surface antigenic markers. Cross-correlation of the data obtained from a complete series of successive two-parameter analyses revealed the existence of about 11 discrete subsets, falling into four-main groups, within the Ly-2-L3T4- population. All subsets consisted of relatively large lymphoid cells. The most numerous group of Ly-2-L3T4- cells was Ly-1 low B2A2-M1/69 high Thy-1 high Pgp-1 low and by these markers resembled Ly-2+L3T4+ cortical blasts. Many of the cells in this group were positive for the IL-2R and/or for MEL-14. A second major group of Ly-2-L3T4- cells was Ly-1 high B2A2-M1/69 low Pgp-1 high, and resembled in some respects activated mature T cells. This group had previously been shown to be absent from the embryonic thymus. The group could be divided into Thy-1 high and Thy-1 low subsets. None of the cells in this group were positive for the IL-2R and very few expressed MEL-14. A third group, 13% of the Ly-2-L3T4- population, was Ly-1 low B2A2-M1/69 low Pgp-1 high, and could also be divided into Thy-1 high and Thy-1 low subsets. A final minor group, 9% of the Ly-2-L3T4- population, was Ly-1 high B2A2-M1/69 high Pgp-1 low Thy-1 high. The particular pattern of markers on these subsets, combined with subsequent information on their properties, makes it unlikely that they all represent sequential steps in one continuous developmental stream, and indicates that complex developmental steps have occurred, even at this supposedly early stage of T cell differentiation.