bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA‐G: expression in human keratinocytes in vitro and in human skin in vivo
Authors: Ulbrecht Matthias , Rehberger Bernd , Strobel Isolde , Messer Gerald , Kind Peter , Degitz Klaus , Bieber Thomas , Weiss Elisabeth H. 
Published: March 2007

AbstractClassical, polymorphic major histocompatibility complex class I molecules are expressed on most nucleated cells. They present peptides at the cell surface and, thus, enable the immune system to scan peptides for their antigenicity. The function of the other, nonclassical class I molecules in man is controversial. HLA‐G which has been shown by transfection experiments to be expressed at the cell surface, is only transcribed in placental tissue and in the fetal eye. Therefore, a role of HLA‐G in the control of rejection of the allogeneic fetus has been discussed. We found that HLA‐G expression is induced in keratinocytes by culture in vitro. Three different alternative splicing products of HLA‐G can be detected: a full length transcript, an mRNA lacking exon 3 and a transcript devoid of exon 3 and 4. Reverse transcription followed by polymerase chain reaction also revealed the presence of HLA‐G mRNA in vivo in biopsies of either diseased or healthy skin.
A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha
Authors: Wilson Anthony G. , Gordon Caroline , di Giovine Francesco S. , de Vries Niek , van de Putte Leo B. A. , Emery Paul , Duff Gordon W. 
Published: March 2007

AbstractWe have investigated the significance of tumor necrosis factor alpha (TNF‐α) polymorphism in relation to systemic lupus erythematosus (SLE) and autoantibody production. Typing of HLA‐B, ‐DR and TNF was performed in 81 Caucasian SLE patients and 168 Caucasian controls. The presence of anti‐Ro and anti‐La antibodies was also determined in patients. The frequency of the TNF2 allele increased in SLE compared with controls [0.24 vs. 0.17, p = 0.04, odds ratio (OR) = 1.6], as did HLA‐DR3 (0.25 vs. 0.13, p < 0.01, OR = 2.3) and HLA‐B8 (0.23 vs. 0.15, p = 0.02, OR = 2). Although HLA‐DR3 showed the strongest disease association, we could not demonstrate association of HLA‐DR3 or TNF2 with SLE independently of each other. Within SLE a much stronger association of TNF2 was seen with autoantibody production: anti‐Ro antibody (0.39 vs. 0.16, p < 0.001, OR = 3.4) and anti‐La antibody (0.43 vs. 0.19, p < 0.001, OR = 3.2). When analyzed independently of each other, however, HLA‐DR3 remained significantly associated with autoantibodies, while TNF2 did not. These data suggest that on the B8‐DR3 haplotype, TNF‐α polymorphism may play a role in SLE susceptibility, but it is not primarily associated with autoantibody production.
Generation of mature T cell populations in the thymus: CD4 or CD8 down‐regulation occurs at different stages of thymocyte differentiation
Authors: Marodon Gilles , Rocha Benedita 
Published: March 2007

AbstractWe have studied the differentiation and repertoire selection during the maturation of CD4+CD8+ (DP) thymocytes into CD4+CD8‐ (CD4SP) and CD8+CD4‐ (CD8SP) T cells, in normal mice, mice transgenic for T cell receptor (TcR)‐αβ restricted by either class I or class II major histocompatibility (MHC), and in mice deficient in class I or class II MHC expression. Our data suggest that mature CD4 and CD8 T cells derive from different pathways of T cell differentiation in the thymus. Thus, interaction of DP thymocytes with MHC class II leads to the immediate down‐regulation of CD8, which occurs simultaneously with an increase in TcR expression; DPTcRloHSAhi thymocytes mature into a CD4+CD8lo TcRhiHSAhi intermediate population. This cell population generates CD4SP thymocytes, the majority of which are still HSAhi. In contrast, interaction with MHC class I induces the up‐regulation of TcR, which precedes the down‐regulation of CD4; DPTcRlo generate DPTcRhi thymocytes, the majority of which are the committed precursors of CD8SP cells. Further differentiation results in CD4 down‐regulation and the transition from DPTcRhi into CD8+CD4lo TcRhiHSAlo and CD8SPTcRhiHSA‐ T cells. Since down‐regulation of CD4 and CD8 occurs at different stages of thymocyte differentiation, our results do not support a stochastic/selective model of lineage commitment in the thymus.
Skin disease‐related T cells bind to endothelial selectins: expression of cutaneous lymphocyte antigen (CLA) predicts E‐selectin but not P‐selectin binding
Authors: Rossiter Heidemarie , Van Reijsen Frank , Mudde Geert C. , Kalthoff Frank , Carla A. F. M. , Bruijnzeel‐Koomen  , Picker Louis J. , Kupper Thomas S. 
Published: March 2007

AbstractCutaneous lymphocyte antigen (CLA), defined by the HECA‐452 antibody, is a cell surface glycoprotein found on a subset of T cells in peripheral blood that binds specifically to E‐selectin. This marker is present on the majority of T cells at sites of cutaneous inflammation and immune responses. Based upon such evidence, an association between T cell CLA expression and skin homing has been proposed. To understand better this relationship, we asked whether putative disease‐related, antigen‐specific T cells expressed CLA. In this study, we employed T helper type 2 (TH2) T cell clones specific for house dust mite (Dermatophagoides pteronyssinus) antigens. These cells were derived from challenged skin of an individual known to react positively to epicutaneous challenge with this agent. In this study, we show that these cloned T cells showed very high homogeneous expression of CLA (nearly 500‐fold higher than T cell clones derived from peripheral blood) and bound specifically to recombinant E‐selectin. The CLA molecule on these cells was identified not only by HECA‐452, but also by CSLEX‐1, indicating that it contained sialyl‐Lex (S‐Lex) determinants. T cells cloned under similar conditions from peripheral blood were CLA negative or low and bound poorly to E‐selectin. Surprisingly, both skin and blood clones bound comparably to P‐selectin. This binding was independent of S‐Lex or CLA expression. We conclude that in sensitized individuals, antigen‐specific T cells expressing high levels of CLA localize in skin promptly after epicutaneous challenge. This localization is likely to involve the interaction of S‐Lex determinants on the CLA molecule with E‐selectin on the dermal microvasculature. We further conclude that T cells can interact with P‐selectin on endothelium and that S‐Lex does not appear to be necessary for this interaction.
Granzyme B and perforin can be used as predictive markers of acute rejection in heart transplantation
Authors: Legros‐Maïda Sabine , Soulié Annie , Benvenuti Christophe , Wargnier Alain , Vallée Nathalie , Berthou Christian , Guillet Jacqueline , Sasportes Marilyne , Sigaux Nicole 
Published: March 2007

AbstractWe have investigated perforin and granzyme B expression in graft‐infiltrating lymphocytes of patients who underwent heart transplantation. Those proteins are commonly present in the cytoplasmic granules of cytotoxic T lymphocytes and are released upon effector‐target cell interaction. From 28 patients 103 endomyocardial biopsies were obtained and examined by histology and immunocytochemical analysis using relevant monoclonal antibodies. We found that “high” biopsy histological grades were associated with perforin and granzyme B expression in graft‐infiltrating lymphocytes of patients with acute severe rejection crisis. In contrast, these markers were not detected in patients without rejection or during graft stabilization. Interestingly, in patients with mild rejection and “low” histological grades, two groups could be distinguished with a differential expression of the two intracytoplasmic proteins. The presence of perforin and granzyme B‐expressing cells was found to be predictive of rapid progression to severe rejection, so that this situation required additional treatment; in contrast, their absence seemed to correlate with a good graft outcome without additional treatment. Moreover, perforin and granzyme B expression seemed to be down‐regulated by immunosuppressive drugs, which coincided with graft stabilization. In conclusion, our data suggest that detection of granzyme B and perforin in graft‐infiltrating lymphocytes might be helpful for routinely monitoring heart transplant patients.
Early events in the assembly of major histocompatibility complex class II heterotrimers from their free subunits
Authors: Nijenhuis Marga , Neefjes Jacques 
Published: March 2007

AbstractEndogenous antigen presentation by major histocompatibility complex class II molecules can be understood if class II αβ heterodimers bind peptide in the endoplasmic reticulum (ER) before they associate with the invariant chain (Ii). We have studied the assembly of class II molecules from the free α, β and Ii subunits to examine the existence of a class II αβ heterotrimer as an intermediate in the assembly of class II αβIi heterotrimers in the ER. In human kidney cell transfectants, the free class II α and β subunits and the class II αβ heterodimer are retained in the ER by association with the chaperonin immunoglobulin binding protein (BiP) and Ii is retained through its cytoplasmic tail. Co‐expression of Ii results in release of BiP from class II αβ complexes and exit of class II αβIi heterotrimers from the ER. We show that the cytoplasmic tail and the transmembrane region of the class II α and β chain is not essential for proper assembly of the class II αβ heterodimer. We followed assembly of the class II αβIi heterotrimers in wild‐type cells. The class II subunits assemble post‐translationally. No class II αβ heterodimers could be isolated as intermediates in the formation of class II αβIi heterotrimers, suggesting that peptide binding by class II molecules in the ER is necessarily inefficient.
Discrete early pro‐B and pre‐B stages in normal human bone marrow as defined by surface pseudo‐light chain expression
Authors: Guelpa‐Fonlupt Valérie , Tonnelle Cécile , Blaise Didier , Fougereau Michel , Fumoux Francis 
Published: March 2007

AbstractVpre‐B and δ‐like genes are selectively expressed in B cell precursors and encode polypeptide chains associated in a m̈‐pseudo light chain (m̈‐PSL) complex which is thought to regulate some early steps of B cell differentiation. We have generated anti‐Vpre‐B monoclonal antibodies which allowed us to identify different steps of differentiation from the pro‐B to the immature B cells by following surface expression of Vpre‐B, m̈ and light chains in normal adult human bone marrow. Already present at the surface of a small fraction of B cell progenitors (CD34+/CD19+) the Vpre‐B molecule was consistently found coexpressed with CD19 and was also found with the sequentially occurring CD10, CD20, CD21, CD22 and CD5 markers. Three discrete cell types were identified: (i) a subpopulation expressing Vpre‐B without m̈ and which represented an early stage of differentiation, (ii) a minor subpopulation co‐expressing Vpre‐B and m̈ without the conventional light chains and (iii) a major subpopulation co‐expressing Vpre‐B, m̈ and χ or δ chains, considered an intermediate pre‐B/B stage. The presence of the PSL chain in various cell subpopulations, in possible association with discrete molecules and/or different contexts, suggests its involvement at several steps of early B cell differentiation.
Cytokines induce lymphocyte migration in vitro by direct, receptor‐specific mechanisms
Authors: Pleass Robert , Camp Richard 
Published: March 2007

AbstractSeveral cytokines have been found to induce human peripheral blood lymphocyte (PBL) migration in vitro. The mechanisms involved are unclear, therefore experiments were carried out to determine whether PBL migration in response to selected cytokines is due to a direct effect, or to the generation of nonspecific secondary mediators, and whether migration is receptor specific. Purified human PBL were incubated with the lymphocyte chemotactic cytokines interleukin (IL)‐1α and IL‐8, followed after 30‐‐60 min by addition of specific neutralizing monoclonal antibody. Supernatants of these mixtures were shown by subsequent assay to be devoid of PBL attractant activity, whereas positive control supernatants containing no antibody induced dilution‐related migration. Addition of antibody to the high affinity IL‐2 receptor abolished the potent attractant effect of IL‐2 on PBL, but had little effect on responses to IL‐1α and IL‐8. These results demonstrate that the in vitro locomotor responses of human PBL to selected cytokines are due to direct, receptor‐specific effects and are not dependent upon the generation of secondary mediator(s).
Development and proliferation of lymphocytes in mice deficient for both interleukins‐2 and ‐4
Authors: Sadlack Benjamin , Kühn Ralf , Schorle Hubert , Rajewsky Klaus , Müller Werner , Horak Ivan 
Published: March 2007

AbstractInterleukin (IL)‐2 and IL‐4 are considered as important regulators of growth and differentiation of lymphocytes. We report that in mice made deficient for both IL‐2 and IL‐4 by gene targeting all major T cell subsets and B cells were normal, indicating that IL‐2 and IL‐4 are not essential for development of the immune system. Paradoxically, proliferation of T cells was increased in both IL‐2‐ and IL‐4‐deficient homozygous mice.
Tolerance induction as a multi‐step process
Authors: Schönrich Günther , Alferink Judith , Klevenz Alexandra , Küblbeck Günter , Hämmerling Günter J. , Arnold Bernd , Auphan Nathalie , Schmitt‐Verhulst Anne‐Marie 
Published: March 2007

AbstractTolerant T cells are characterized by their partial or full resistance to activation by antigen. We investigated whether tolerant T cells were still receptive to further tolerogenic signals. T cells expressing a transgenic T cell receptor (TCR) specific for the major histocompatibility complex (MHC) class I molecule Kb were deleted in mice carrying Kb but not in mice expressing the mutant Kb‐molecule Kbm1 [TCR (H‐2bm1 × k) mice]. These T cells were tolerant in vivo but could be activated in vitro by the Kb antigen. This in vitro reactivity was abolished after the tolerant T cells encountered Kb‐positive cells that had been intravenously injected. Furthermore, in TCR (H‐2bm1 × k), mice expressing Kb only on hepatocytes, no T lymphocytes bearing the transgenic TCR could be found in the periphery, indicating that the additional contact with Kb on hepatocytes led to deletion of the tolerant T cells. These findings demonstrate that tolerance induction can be a multi‐step process.
The envelope glycoprotein of HIV‐1 gp120 and human complement protein C1q bind to the same peptides derived from three different regions of gp41, the transmembrane glycoprotein of HIV‐1, and share antigenic homology
Authors: Stoiber Heribert , Ebenbichler Christoph , Dierich Manfred P. , Thiele Nicole M. , Arlaud Gerard J. 
Published: March 2007

AbstractGp41, the transmembrane glycoprotein of HIV‐1, has been shown to be non‐covalently associated with gp120. We have shown that it also binds human C1q. To analyze the interaction site(s) of gp41 with these two molecules, we established an enzyme‐linked immunosorbent assay (ELISA) system using recombinant soluble gp41 [amino acids (aa) 539–684] and peptides thereof. In the cell‐external part of gp41 three sites (aa 526–538, aa 590–613 and aa 625–655) were found to bind both gp120 and C1q. That gp120 and C1q use the same sites was evidenced by the fact that these proteins competed with each other for the same sites in recombinant soluble gp41 and gp41 peptides. It could be demonstrated by ELISA, that rabbit antibodies against human C1q recognized gp120, and rabbit antibodies against gp120 cross‐reacted with C1q. Rabbit anti‐gp120, HIV‐1‐positive human sera and anti‐gp120 obtained from such sera agglutinated sensitized sheep erythrocytes with human C1q (EAC1q).These data suggest that in addition to functional homology between C1q and gp120 structural homology between these two molecules exists. This molecular mimicry might become the basis for immunologically relevant autoimmune phenomena.
Neuronal interferon‐γ immunoreactive molecule: Bioactivities and purification
Authors: Olsson Tomas , Bakhiet Moiz , Höjeberg Bo , Ljungdahl Åke , Kelic Sofija , Edlund Conny , Kristensson Krister , Van Der Meide Peter H. 
Published: March 2007

AbstractAn interferon (IFN)‐γ immunoreactive molecule, localized to small neurons in peripheral sensory ganglia (N‐IFN‐γ), has been detected with two mouse monoclonal antibodies (DB1 and DB16) directed against different epitopes of rat IFN‐γ. To define N‐IFN‐γ with regard to its protein characteristics and bioactivities, DB1 and DB16 were used to purify N‐IFN‐γ from rat trigeminal ganglia in a two‐step sequential antibody‐affinity procedure. Sodium dodecylsulfate polyacrylamide gel electrophoresis (PAGE) and silver staining of purified N‐IFN‐γ displayed three bands with an approximate molecular mass of 66, 62 and 54 kDa. The N‐IFN‐γ bioactivity was confined to the protein stained on gel when native material was run on PAGE. Biological effects of pure N‐IFN‐γ were examined and compared with those of lymphocyte‐derived recombinant IFN‐γ. N‐IFN‐γ had antiviral effects in vitro and induced major histocompatibility complex class I and II antigens on macrophages and in cells in skeletal muscle cell cultures. N‐IFN‐γ also stimulated myoblast proliferation and affected cholinergic receptor distribution on myotubes similar to recombinant IFN‐γ. Both molecules potently stimulated Trypanosoma brucei brucei growth. These data suggest that, although N‐IFN‐γ is a protein distinct from lymphocyte‐derived IFN‐γ, the two molecules have enough structural similarities to allow for antibody recognition of at least two epitopes, and action on similar target structures on both parasite and mammalian cells.
Murine epidermal Langerhans cells and splenic dendritic cells present tumor‐associated antigens to primed T cells
Authors: Cohen Philip J. , Cohen Peter A. , Rosenberg Steven A. , Mulé James J. , Katz Stephen I. 
Published: March 2007

AbstractWe examined the ability of epidermal Langerhans cells and splenic dendritic cells to present tumor‐associated antigens (Ag) to immune T cells. Methylcholanthrene (MCA)‐induced subcutaneous fibrosarcomas derived from C57BL/6 mice were used as tumor models. Our data demonstrate that both murine Langerhans cells and splenic dendritic cells have the capacity to present tumor‐associated Ag to primed T cells. We found that variously treated tumor preparations (irradiated viable tumor cells, irradiated frozen‐stored tumor cells, mitomycin C‐treated viable tumor cells, and snap freeze‐thawed tumor cell lysates) can be utilized for tumor Ag‐pulsing. Primed CD4+ T cells demonstrated in vitro specificity towards their respective tumors and did not cross‐react to other syngeneic MCA‐induced or non‐MCA‐induced tumors. The T cell proliferative response critically depended on the presence of immune CD4+ T cells. We discuss the implications of these findings for the adoptive immunotherapy of cancer using immune CD4+ T cells.
Identification of an HLA‐DQ2 peptide binding motif and HLA‐DPw3‐bound self‐peptide by pool sequencing
Authors: Verreck Frank A. W. , van de Poel Anja , Termijtelen Annemarie , Drijfhout Jan‐Wouter , Koning Frits , Amons Reinout 
Published: March 2007

AbstractMolecules of the major histocompatibility complex (MHC) present antigenic peptides to T cells. Sequencing peptide pools eluted from MHC class I molecules has established allele‐specific peptide binding motifs. We applied pool sequencing to analyze human MHC class II‐bound peptides and found that HLA‐DQ2‐eluted peptides predominantly contained lysine, isoleucine, and phenylalanine at relative position i, i + 3 and i + 8, respectively. These residues putatively represent anchor residues for MHC binding. Analysis of a heterogeneous HLA‐DPw3/DPw4‐eluted peptide pool yielded a sequence matching an epitope from the endogeneous enzyme glyceraldehyde‐3‐phosphate dehydrogenase. This self‐peptide and a partially identical, known allo‐epitope bound specifically to DPw3 and DR13 molecules, suggesting the sharing of a binding motif. In particular, the presence of an arginine at relative position 4 appeared important for binding to these HLA class II specificities. Thus, pool sequencing is applicable for the analysis of MHC class II‐eluted peptides.
A quantitative assay to measure the interaction between immunogenic peptides and purified class I major histocompatibility complex molecules
Authors: Olsen Anna Catharina , Pedersen Lars ØStergaard , Hansen Anette Stryhn , Buus Søren , Nissen Mogens Holst , Olsen Marianne , Hansen Paul Robert , Holm Arne 
Published: March 2007

AbstractA direct and sensitive biochemical assay to measure the interaction in solution between peptides and affinity‐purified major histocompatibility complex (MHC) class I molecules has been generated. Specific binding reflecting the known class I restriction of cytotoxic T cell responses was obtained. Adding an excess of β2‐microglobulin (β2m) significantly increased the rate of peptide association, but it did not affect the rate of dissociation. Binding was complicated by a rapid and apparently irreversible loss of functional MHC class I at 37°C which might limit the life span of empty MHC class I thereby preventing the inadvertent exchange of peptides at the target cell surface. All class I molecules tested bound peptides of the canonical octa‐ to nona‐meric length. However, one class I molecule, Kk, also bound peptides, which were much longer suggesting that the preference of class I molecules for short epitopes is not absolute and may be caused by factors other than the peptide‐MHC class I binding event itself.
Transcriptional regulation of the gene for the second component of human complement: Promoter analysis
Authors: Sullivan Kathleen E. , Valle David , Winkelstein Jerry A. , Wu Lai‐Chu , Campbell R. Duncan 
Published: March 2007

AbstractThe 5′ flanking region of the human gene for the second component of complement was sequenced and analyzed functionally. RNase protection demonstrated a cluster of four initiation sites in the 5′ flanking region utilized in the hepatoma cell line, HepG2. Utilization of all four initiation sites increased in response to γ‐interferon (IFN‐γ). Transient transfection analysis was used to examine cis‐acting sequence motifs controlling transcription from the 5′‐flanking region. We identified a 228‐bp minimal promoter fragment which was able to direct basal and IFN‐γ inducible transcription from authentic initiation sites. Sequence motifs outside of this region may modulate the transcriptional regulation of the second component of complement. Although complement components are not coordinately regulated, we identified four regions of significant homology with the promoters of multiple other complement components. Three of these regions were within the minimal promoter fragment.
A new mutation, aly, that induces a generalized lack of lymph nodes accompanied by immunodeficiency in mice
Authors: Miyawaki Shigeki , Nakamura Yutaka , Suzuka Hirotsugu , Koba Masahiro , Shibata Yoshihisa , Yasumizu Ryoji , Ikehara Susumu 
Published: March 2007

AbstractWe have found a new spontaneous autosomal recessive mutation in mice that causes a systemic absence of lymph nodes and Peyer's patches. The name “alymphoplasia”, with the gene symbol “uly”, is proposed for this mutant. The spleen of alylay mice is devoid of well‐defined lymphoid follicles, and the thymus does not show a clear cortical‐medullary distinction. The mutant homozygotes are deficient in both humoral and cell‐mediated immune functions, and are highly susceptible to infections. They have a reduced level of IgM and severely depressed levels of IgG and IgA in their sera, and do not reject allogeneic skin grafts. However, they have mature T and B cells as determined from their cell surface antigens. The results of bone marrow transplantation experiments suggest a mesenchymal disorder as a possible cause of the lack of lymph nodes and of immunodeficiency in the aly mouse. The aly mutant mouse may be a useful animal model of primary immunodeficiency, as are the nu (nude) and scid (severe combined immunodeficiency) mice.