bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Ig superfamily CTLA‐4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA‐4 cytoplasmic domains
Authors: Dariavach Piona , Mattéi Marie‐Geneviève , Golstein Pierre , Lefranc Marie‐Paule 
Published: March 2007

AbstractThe mouse CTLA‐4 gene has been shown to code for an activated lymphocyte‐associated sequence belonging to the Ig gene superfamily. We now report on the molecular cloning and study of the human corresponding gene isolated from a genomic library and designated Hu‐CTLA‐4. The Hu‐CTLA‐4 gene exists as a single copy per human haploid genome and maps to band q33 of chromosome 2. It comprises 3 exons notwithstanding the leader sequence. The first exon encodes a V‐like domain of 116 amino acids, the second one a hydrophobic putative transmembrane region of 37 amino acids and the third one a 34 amino acid putative cytoplasmic domain. Whereas the overall homology between the human and murine CTLA‐4 proteins is 76%, there is, remarkably, a complete identity of their cytoplasmic domains. This complete interspecies conservation comes in support of an important role for this domain in CTLA‐4 function.
Molecular analysis of T cell receptor gamma gene expression in allo‐activated splenic T cells of adult mice
Authors: Jones Barry , Carding Simon , Kyes Susan , Mjolsness Shelley , Janeway Charles , Hayday Adrian 
Published: March 2007

AbstractNorthern analysis, hybridization in situ and cDNA sequence analysis have been used to demonstrate that the induction of T cell γ‐gene expression is a general occurrence when primary splenic T cells of adult mice are cultured in short‐term mixed lymphocyte reactions (MLR). Splenic T cells from nine strains of mice examined in eleven different MLR all showed significant induction of γ‐RNA, even when the primary T cell response was to only a three amino acid mismatch in a major histocompatibility complex class I antigen. In MLR examined in detail, the expression is highly enriched for in CD3+ “double‐negative” T cells (lacking both CD4 and CD8 expression). A cDNA sequence analysis, constituting the first such analysis of any size of γ‐gene transcripts from circulating, peripheral cells of adult mice, revealed transcription to be frequently of productively rearranged genes. These genes display extensive junctional diversity.
Tolerization during pregnancy: impact on the development of antigen‐specific help and suppression
Authors: Zöller Margot 
Published: March 2007

AbstractAnalysis of splenic B cells in the offspring of BALB/c mice which were treated with 2,4,6‐trinitrobenzenesulfonic acid (TNBS) throughout the gestational period revealed that reduced responsiveness was predominantly reflecting changes in regulatory cells. Since development of T cells takes place in the thymus, postnatal maturation of helper (Th) and suppressor (Ts,) T cells was evaluated in the thymus as well as in the spleen. To elaborate the impact of prenatal TNBS‐treatment on the trinitrophenyl (TNP) repertoire, TNP‐sheep red blood cell‐ and fluorescein isothiocyanate‐specific regulatory elements were determined in parallel. It was found that the thymus contained activated helper and suppressor cells during the first 2 weeks of postnatal life, the majority of which appeared to be self‐specific. Self reactivity in thymus and periphery disappeared within 3 weeks. Prenatally TNBS‐treated mice differed in as much as they apparently recognized TNP‐self as a self component, TNP‐self reactivity being down‐regulated similar to self reactivity in prenatally untreated mice. This explains why prenatally TNBS‐treated mice responded poorly to stimulation with conventional T‐dependent TNP‐carrier conjugates. Yet, they responded transiently to TNP‐anti‐TNP conjugates. It could be shown that this was due to down‐regulation of putatively idiotype‐specific Tswhich were highly increased in prenatally TNBS‐treated mice. Data are interpreted in the sense that the establishment of self tolerance is preceded by activation of self‐reactive Th, which become partially eliminated. Remaining autoreactivity is controlled by the establishment on an equilibrium between idiotypic and anti‐idiotypic elements.
Modulation on immunogenicity by HLA‐B27 subtype polymorphism
Authors: Jaraquemada Dolores , Galocha Begoña , Aparicio Pedro , Rojo Susana , And Victor Calvo , Castro José A.LÓPez De 
Published: March 2007

AbstractCells from the same HLA‐B27− individual, PA, were stimulated in vitro in primary mixed lymphocyte culture, with either B*2705+ or B*2704+ lymphoblastoid cell lines, in independent experiments. Cytolytic T lymphocytes (CTL) were cloned at limiting dilution and the clones obtained were screened for anti‐B27 alloreactivity. Most of the CTL clones generated against the B*2705+ stimulator cells were directed against the B*2705 +antigen. In contrast, no anti‐B27 CTL clones were found among those derived against the B*2704+ stimulator cells. This was not due to a poor cytotoxic response against these cells because a large proportion of the T cell clones derived from this stimulation were cytotoxic. B2704 differs from B705 by only two amino acid changes at positions 77 and 152. Previous studies (Aparacio, P. et al., Eur. J. Immunol. 1988. 18:203) have shown that none of the anti‐B*2705 CTL clones derived from donor PA and amenable to detailed characterization cross‐reacted with B*2704, suggesting that most of this cytotoxic response was directed against an immunodominant determinant contributed for by residues 77 and/or 152 from B*2705. The present results further suggest that the changes at these positions in B*2704 alter this determinant in such a way that B*2704 becomes less immunogenic for the particular individual PA. Furthermore, a similar poor anti‐B*2704 CTL response was obtained from a second B27− responder individual, AE, stimulated with another B2704+ cell line. The single anti‐B*2704 CTL clone, 64.8P, isolated from this second individual, displayed an unusual reaction pattern in that it cross‐reacted with all B27 subtypes with changes only at or close to positions 77 and 152, including B*2705. Significantly, the only HLA‐B27 subtype that was not recognized by CTL 64.8P was B*2703, which differs from B*2705 only at residue 59. This residue is located in the three‐dimensional structure at the opposite end from residues 77 and 152 at the surface of the antigen‐binding groove of the class I molecule. Thus, the area around residues 77 and 152 is not an essential part of the epitope recognized by CTL 64.8P.
Glucocorticosteroid‐dependent synergy between interleukin 1 and interleukin 6 for human B lymphocyte differentiation
Authors: Emilie Dominique , Crevon Marie‐Claude , Auffredou Marie Thérèse , Galanaud Pierre 
Published: March 2007

Abstract In order to analyze the effects of interleukin (IL) 6 on human in vitro Ig production B lymphocytes were activated by Staphylococcus aureus Cowan strain I (SAC) in the presence of low concentrations of IL2 (1 U/ml) and dexamethasone (10−7 M). Previously we showed that this model of B cell response is completely monocyte dependent. We here demonstrate that, under these experimental conditions, IL6 is able to replace monocytes and stimulate Ig production provided IL1 is also present. Dose‐effect curves show that these two monokines act synergistically. This synergy is demonstrable only in the presence of dexamethasone, when B lymphocytes are activated (by SAC) and when T cell help (provided by IL2) is present. It results in the production of both IgM and IgG. Both IL 1 and IL6 have to be present during the first 48 h of culture to exert an optimal effect. These results show that IL6 may act on early (as well as on late) stages of normal B lymphocyte differentiation. Moreover, glucocorticosteroids potentiate the synergistic effect of IL1 and IL6 on their B lymphocyte target, an effect comparable to that exerted on hepatocytes.
At least three distinct B cell epitopes reside in the C‐terminal half of La protein, as determined by a recombinant DNA approach
Authors: Rauh Andreas Johann Gallus , Hornig Horst , Lührmann Reinhard 
Published: March 2007

Abstract The La antigen is a nuclear protein that is one of the major target antigens of autoantibodies found in the sera of patients with primary Sjögren's syndrome. The formation of such autoantibodies is therefore likely to reflect the basic immunopathogenesis of this disorder. A recombinant DNA strategy has been used to examine the La protein for sequences that encode autoimmunizing B cell epitopes. We have isolated and characterized a 1.2‐kb‐long cDNA from a human liver cDNA library encoding a region of the La protein; this region contains 296 amino acids, including the C terminus. A sub‐library of recombinant DNA in the expression vector pEX was made from portions of the La cDNA. Individual fusion proteins were tested by immunoblotting and enzyme‐linked immunosorbent assay for their ability to react with anti‐La autoantibodies contained in sera from patients with Sjögren's syndrome. In this way, we have identified at least three distinct epitopes in the C‐terminal half of the La protein. Every anti‐La serum tested contained antibodies against all three of the antigenic regions identified. Furthermore, most of the sera display similar ratios between the titers of antibodies with the three kinds of specificity. Our data suggest that the production of anti‐La autoantibodies may be antigen driven.
Functional and biochemical characterizations of avian T lymphocyte antigens identified by monoclonal antibodies
Authors: Lillehoj Hyun Soon , Lillehoj Erik Peter , Weinstock Daniel , Schat Kaiel Antoni 
Published: March 2007

Abstract Seven monoclonal antibodies (mAb) were used to characterize antigens present on chicken T lymphocytes and on natural killer cells by flow cytometry, radioimmunoprecipitation and by effects on cell‐mediated cytotoxicity and mitogen‐induced proliferation. mAb CTLA8 and 5 stained 73% of thymus, 44% of spleen and 51% of peripheral blood lymphocytes (PBL), respectively, and immunoprecipitated 65‐ and 45‐kDa proteins from detergent extracts of 125I surface‐labeled thymocytes. Pretreatment of splenic lymphocytes with mAb CTLA5 and 8 in the presence of rabbit complement (C) eliminated the concanavalin A (Con A)‐induced T cell proliferative responses. mAb CTLA3, 4 and 9 stained 43% of thymus, 36% of spleen and 18% of PBL, and immunoprecipitated 33–35‐kDa proteins. Pretreatment of spleen cells with mAb 4 or 9 plus C reduced, but did not eliminate, the Con A‐induced proliferative response and significantly reduced both major histocompatibility complex (MHC)‐restricted and non‐MHC‐restricted cellular cytotoxicity. mAb CTLA1 and 6 stained 58% of thymus, 13% of spleen and 19% of PBL. mAb CTLA 1 and 6 immunoprecipitated a 65‐kDa protein. mAb CTLA l and 6 had no effect on the Con A‐induced blastogenesis and CTLA 6 caused no decrease in virus‐specific cytotoxic T lymphocyte and natural killer activity. These results indicate that (a) mAb CTLA 5 and 8 identify antigens on mature T lymphocytes that are similar in tissue distribution, molecular mass and function to the mammalian CD5 antigen; (b) mAb CTLA 3, 4 and 9 detect the avian homologue of CD8 antigen; and (c) mAb CTLA l and 6 identify the avian homologue of CD4 antigen.
Human IgG and IgA subclass response following immunization with a polyvalent Klebsiella capsular polysaccharide vaccine
Authors: Cryz Stanley J. , Cross Alan S. , Sadof Gerald C. , Que John U. 
Published: March 2007

AbstractThe human IgG and IgA response was determined after vaccination with an experimental 24‐valent Klebsiella capsular polysaccharide vaccine. The majority of natural antibody acquired prior to immunization was found in the IgG1, IgG2 and IgA1 subclasses. The immune response to vaccination was concentrated within the IgG1, IgG2, IgA1, and IgA2 subclasses with > 70% of subjects responding with a significant (2 fourfold) rise in titer. The IgG3 and IgG4 response was meager with few volunteers (0%‐40%) showing a significant titer rise. Therefore, vaccination with Klebsiella capsular polysaccharide induces a vigorous IgG and IgA response in humans which is not restricted to single antibody class or subclass.
Tumor necrosis factor α stimulates leukotriene production in vivo
Authors: Huber Michael , Beutler Bruce , Keppler Dietrich 
Published: March 2007

AbstractTumor necrosis factor α, or cachectin (TNF), is a polypeptide mediator with proinflammatory and antitumor actions. It is produced in large amounts by lipopolysaccharide (LPS)‐activated macrophages. TNF as well as LPS stimulated the arachidonate cascade leading to the synthesis of leukotrienes (LT) in vivo. Production of endogenous cysteinyl LT was measured in anesthetized rat using the biliary excretion of N‐acetyl‐LTE4 as an indicator. Infusion of TNF over a 1‐h period greatly increased the rate of cysteinyl LT prodcution during the subsequent 3 h. Pretreatment with anti‐TNF antibody F(ab′)2 fragments prevented enhanced LT generation as well as tachypnea (a sign of the in vivo action of TNF). LT production elicited by TNF was similar to that evoked by infusion of LPS. Our results indicate that lipoxygenase products are involved in the network of pathophysiological events induced by TNF. The proinflammatory and shock‐inducing LT may mediate many of the adverse effects of TNF in vivo as well as its antitumor action.
Cross‐linking of the T cell antigen receptor interferes with the generation of CD4+8+ thymocytes from their immediate CD4−8+ precursors
Authors: Hünig Thomas 
Published: March 2007

AbstractThe majority of thymocytes are immature cells co‐expressing the surface markers CD4 and CD8. About two thirds of these cells also express the T cell antigen receptor (TcR), though at a level distinctly lower than found on mature T cells. The direct precursors of these “double‐positive” thymocytes are cycling cortical blast cells of the CD4−8+ phenotype. Using a new monoclonal antibody to a constant determinant of the rat TcRα/β, it is shown here that (a) about 50% of these CD8 “single‐positive” committed precursor cells already express the TcRα/β, though at very low levels, (b) during short‐term suspension culture in medium supplemented only with fetal calf serum they not only acquire CD4 but also TcRα/β levels characteristic of CD4,8 “double‐positive” thymocytes, and (c) cross‐linking of the TcR during culture inhibits the acquisition of the CD4 antigen in the majority of these cells.
The tumor progression‐associated human melanoma antigen P3.58 mediates monocyte‐lymphocyte interactions in vitro
Authors: Johnson Judith P. , Lehmann Jurgen M. , Riethmiiller Gert 
Published: March 2007

AbstractThe melanoma‐associated antigen P3.58 is rarely found on benign proliferating melanocytes but is consistently expressed on advanced malignant melanomas which have a high probability of metastasis. Previous studies have shown that its expression on normal tissues is limited to vascular endothelia and lymphoid follicle germinal centers and that it is also expressed by activated monocytes in vitro. In the studies reported here, anti‐P3.58 monoclonal antibodies (mAb) were shown to partially inhibit antigen‐specific and anti‐CD3‐induced T cell proliferation and to completely block a lymphocytelmonocyte clustering which occurs in the absence of added antigen. This inhibition is highly specific for P3.58 mAb and was not affected by mAb directed to major histocompatibility complex or T cell antigens. P3.58 therefore seems to be involved in an antigen‐independent attraction or adhesion of lymphocytes. P3.58 is the second example (HLA‐DR being the first) of an association between the expression of an immune function‐associated molecule and the development of metastatic disease in melanoma.
Identification of a new epitope of the 4F2/44D7 molecular complex present on sarcolemma and isolated cardiac fibers
Authors: Bellone Graziella , Alloatti Giuseppe , Levi Renzo , Geuna Massimo , Tetta Ciro , Peruzzi Licia , Letarte Michelle , Malavasi Fabio 
Published: March 2007

AbstractThe murine monoclonal antibody (mAb) CB43, raised against the K‐562 erythroleukemia line, reacts with monocytes, tissue macrophages, thymocytes and with all the human lines tested but not with resting lymphocytes, large granular lymphocytes, granulocytes and erythrocytes. However, activated lymphocytes and natural killer cells express the CB43 antigen. Embryonic and fetal fibroblasts are positive, while adult fibroblasts are negative. Proximal convoluted tubules in kidney, epithelial cells in esophagus and breast, and sarcolemma in skeletal muscle are reactive with mAb CB43. This antibody can also bind to isolated guinea pig cardiac myocytes, and, furthermore, can induce a transient inotropic effect on isolated atria.The reactivity with different cell and tissue types and the functional effects of the CB43 mAb were reminescent of the 4F2/44D7 antibodies, shown previously to block Na/Ca2+ exchange in heart and skeletal muscle. Co‐immunoprecipitation studies with CB43 and 44D7 mAb, using radiolabeled Daudi cells, revealed co‐migration of polypeptides of 87 and 38 kDa.However, the epitope recognized by CB43 is not present on the human heavy chain which bears the 44D7/4F2 epitope as demonstrated by the lack of reactivity of CB43 mAb with mouse L cells transfected with the 4F2 heavy chain gene. Thus, CB43 represents a newly described epitope present on the human light chain or dependent on the conformation of the human dimer.
Activation of the interleukin 2 pathway precedes CD3‐T cell receptor expression in thymic development. Differential growth requirements of early and mature intrathymic subpopulations
Authors: Toribio María Luisa , Hera Antonio De La , Marcos Miguel A. R. , Márquez Carlos , Martínez‐A Carlos 
Published: March 2007

AbstractT cell activation induced via the CD3‐T cell receptor (TcR) complex, or by triggering of polyclonal antigen‐independent pathways, involves both interleukin 2 (IL 2) production and IL 2 receptor (IL 2R) expression and results in T cell proliferation. To assess the potential role of the IL 2 pathway in T cell development, growth and activation requirements of intrathymic T cell precursors were analyzed and correlated with the expression of IL 2R. In contrast to CD3‐TcR (either CD4 or CD8) mature thymic cells, CD3‐TcR‐ CD1‐4‐8‐ early prothymocytes constitutively expressed IL 2R and displayed IL 2‐mediated proliferation, which was inhibited by anti‐IL 2R monoclonal antibodies (mAb). Moreover, prothymocytes developed spontaneous proliferation in the absence of exogenous IL 2, which was also abrogated by blocking of IL 2R with specific mAb. The possibility that both IL 2 production and IL 2R expression are autonomously activated early in T cell development, before acquisition of the CD3‐TcR complex, led us to study the implication of alternative pathways of activation at this ontogenic stage. Triggering of the CD2 pathway with mAb against two different epitopes of the molecule (D66 and 9.6/T111) induced proliferation of CD3‐TcR‐ prothymocytes in the absence of exogenous IL 2, while proliferation of CD3‐TcR mature thymocytes required IL 2 supplementation. These data suggest that polyclonal activation of the IL 2 pathway may be selectively operative at early stages of T cell development, being involved in the growth and differentiation of intrathymic T cell precursors.
Evidences for protein kinase C. Activation in T lymphocytes by stimulation of either the CD2 or CD3 antigens
Authors: Friedrich Bengt , Cantrell Doreen A. , Gullberg Martin 
Published: March 2007

AbstractPhosphorylation of protein kinase C (PKC) substrates in T lymphocytes was analyzed after stimulation with specific pairs of anti‐CD2 monoclonal antibodies (mAb) or an anti‐CD3 mAb. The results show that the appropriate stimulation of both CD2 or CD3 antigens results in phosphorylation of a 80‐kDa putative PKC substrate and that this phosphorylation event is sensitive to a PKC inhibitor, sphinganine. CD2‐ and CD3‐dependent phosphorylation was found to be strongly dependent on an extensive cross‐linking of surface antigens. The biological importance of cross‐linking of CD2 and CD3 was also evident for other biological responses such as interleukin 2 production and induction of an autocrine growth response. Finally, we also present evidence for interaction between the CD2 and CD3 signal transducing pathways.
Restriction fragment analysis of VpreB and λ5 within the genus Mus
Authors: D'Hoostelaere Lawrence A. , Bauer Steven R. , Melchers Fritz 
Published: March 2007

AbstractDNA from a panel of inbred strains of mice and colony bred mice, isolated from different geographical locations, was hybridized to mouse VpreB and λ5 probes under stringent conditions, indicating sequence similarities greater than 80%. The probe for λ5 detects one gene and the probe for VpreB detects two genes (VpreB1 and VpreB2) in the inbred strains of mice examined under the stringency used. No restriction endonuclease fragment length polymorphisms (RFLP) were detected with the VpreB and λ5 DNA probes among the inbred strains of mice using Bam HI and Hind III. Very few RFLP were detected among Mus musculus subspecies, and the intensity of the hybridization did not differ significantly with either DNA probe. The number of RFLP increased slightly when different species and subgenera were examined, and the intensity of the hybridization signal began to decrease in samples from the different subgenera, suggesting a slight decrease in sequence similarity for both VpreB genes with increased time of divergence. Fewer RFLP were detected with the λ5 DNA probe. DNA from 11 different Mus species representing 4 subgenera, genetically isolated from laboratory mice for approximately 1–12 million years, continued to hybridize under high stringency conditions using both DNA probes. A comigrating λ5 and VpreB restriction endonuclease fragment was detected in most of the samples examined, suggesting the close physical linkage of VpreB1 and λ5 is maintained within the genus Mus. These results suggest that VpreB1, VpreB2 and λ5 have been present for over 12 million years.
Efficient mapping and characterization of a T cell epitope by the simultaneous synthesis of multiple peptides
Authors: Zee Ruurd Van Der , Eden Willem Van , Meloen Rob H. , Noordzij Alie , Van Embden Jan D. A. 
Published: March 2007

AbstractPrediction, identification and analysis of T cell epitopes in protein antigens has become a central theme in fundamental and applied immunology. However, while for the characterization of linear B cell epitopes the so‐called Pepscan procedure was found to be extremely effective, no such technique has so far been available for T cell studies. Recently, we described the identification and localization of a T cell epitope in a mycobacterial 65‐kDa shock protein in the model of adjuvant arthritis. This was done by molecular cloning and conventional solid‐phase synthesis techniques. We now show that the delineation of such a T cell epitope and its further characterization can be accomplished in a much more rapid and efficient manner by a modification of the existing Pepscan technique. We show for the first time that several hundreds of peptides, simultaneously synthesized in an automated way on activated polyethylene rods, can be easily recovered from these rods in adequate quantities, enabling a systematic analysis of T cell epitopes. Synthesis of sequentially overlapping peptides along the 65‐kDa protein revealed that the adjuvant arthritis T cell clones are fully stimulated by peptides that comprise a minimal sequence of seven residues, corresponding to positions 180–186 in the sequence of the 65‐kDa protein of M. bovis Bacillus Calmette Guerain (BCG). Detailed examination of the epitope by peptides containing a single amino acid substitution showed that, apart from one conservative replacement (Glu → Asp), the requirement for the native residue at all positions in peptide 180–186 was absolute for full T cell stimulation. Their indispensability was confirmed with deletion and insertion peptides. It is concluded that the occurrence of indifferent or spacer residues in a minimal stimulatory sequence, as observed by others, is not a general feature of T cell epitopes.