bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional and ligand binding specificity of the rabbit neutrophil IL-8 receptor.
Authors: Thomas K M , Taylor L , Prado G , Romero J , Moser B , Car B , Walz A , Baggiolini M , Navarro J 
Published: December 2022

Abstract
IL-8 mediates migration and activation of neutrophils. This study describes the functional and ligand binding specificity of the human intercrine peptides IL-8, neutrophil-activating peptide 2 (NAP-2), melanoma growth stimulatory activity (GRO), and platelet factor 4 (PF4) to rabbit neutrophils and mammalian cell lines transfected with rabbit IL-8 receptor cDNA (F3R). Rabbit neutrophil membranes bound 125I-labeled IL-8 and 125I-labeled NAP-2 but did not bind 125I-labeled GRO or 125I-labeled PF4. Rabbit neutrophils mobilized intracellular Ca2+ in response to IL-8 and NAP-2 but not to GRO or PF4. Monkey kidney cells (COS-7) and hamster lung fibroblasts (CCL-39) were transiently and stably transfected with the rabbit neutrophil IL-8 receptor F3R cDNA. COS-7 cells transfected with F3R cDNA bound 125I-labeled IL-8 but did not bind other IL-8-related peptides such as 125I-labeled NAP-2, 125I-labeled GRO, or 125I-labeled PF4. Furthermore, bound 125I-labeled IL-8 was only displaced by unlabeled IL-8 but not by unlabeled NAP-2, GRO alpha, or PF4. Consistent with this observation, stably transfected CCL 39 cells expressing F3R cDNA mobilized Ca2+ only in response to IL-8. We conclude that F3R cDNA encodes a functional IL-8 receptor isotype with strict ligand binding specificity for IL-8, that rabbit neutrophils do not bind human GRO alpha, and it is suggested that rabbit neutrophils contain in addition to the F3R protein another IL-8 receptor isotype with broad ligand specificity or a distinct NAP-2 receptor.
Naturally processed peptides longer than nine amino acid residues bind to the class I MHC molecule HLA-A2.1 with high affinity and in different conformations.
Authors: Chen Y , Sidney J , Southwood S , Cox A L , Sakaguchi K , Henderson R A , Appella E , Hunt D F , Sette A , Engelhard V H 
Published: December 2022

Abstract
An equilibrium binding assay was used to directly measure the relative affinities of naturally processed 9-mer, 10-mer, and 12-mer peptides for the human class I MHC molecule HLA-A2.1. The peptides exhibited a range of affinities with IC50 values of 11 to 214 nM. The mode of interaction between these peptides and HLA-A2.1 was examined using peptides in which Asp had been substituted for suspected anchor residues. Regardless of length, the previously identified Leu at position 2 relative to the amino terminus was critical for peptide binding. While the carboxyl terminal residue was also critical for the binding of a 9-mer peptide, it was much less important in the binding of longer peptides. Additional residues close to the carboxyl terminus that contained aliphatic hydrocarbon side chains were of similar or greater importance in peptide binding. In addition, residue at position 3 also appeared to be important for the binding of longer peptides. The data suggest that different naturally occurring longer peptides can bind in different conformations to class I MHC molecules. While one of these is similar to the kinked conformation described by others, another conformation would involve an extension of the carboxyl terminus out of the class I binding site. The ability of MHC molecules to accommodate the same peptide in different conformations would appear to have distinct advantages to the immune system.
T cell determinant structure of myelin basic protein in B10.PL, SJL/J, and their F1S.
Authors: Bhardwaj V , Kumar V , Grewal I S , Dao T , Lehmann P V , Geysen H M , Sercarz E E 
Published: December 2022

Abstract
Recent experiments have shown that during the course of chronic experimental allergic encephalomyelitis, there is a shift in the determinant hierarchy away from the dominant to other subdominant and cryptic self determinants. It was therefore of interest to define the pattern of dominance for mouse myelin basic protein in the three commonly used experimental allergic encephalomyelitis model strains of mice, i.e., B10.PL, SJL/J, and (SJL x B10.PL)F1. Our studies indicate that many cryptic determinants are demonstrable, which only activate T cells on injection as individual peptides and not with the native protein. The core amino acid residues of the various determinants are defined and range in size between 5 and 10 amino acids. Interestingly, there is a bias toward H-2u-restricted response vis-a-vis the H-2s-restricted response in the (SJL x B10.PL)F1 strain. The TCR V beta 8.2 gene segment was not predominantly used for responses to other determinants, although some B10.PL and (SJL x B10.PL)F1 cell lines expressed V beta 8.2 more than others. This study represents the most comprehensive analysis so far of the pattern of dominant and cryptic proliferative T cell determinants and their core sequences for mouse myelin basic protein.
Induction of allograft tolerance in rats by an HLA class-I-derived peptide and cyclosporine A.
Authors: Nisco S , Vriens P , Hoyt G , Lyu S C , Farfan F , Pouletty P , Krensky A M , Clayberger C 
Published: December 2022

Abstract
T cell recognition of MHC molecules initiates a cascade of events resulting in allograft rejection. CTLs damage the graft by targeting nonself-MHC class I molecules. We and others have previously shown that small synthetic peptides corresponding to regions of certain MHC class I molecules can inhibit the CTL response against MHC class I alloantigens in vitro. Here we report that rat heart allografts survived survived indefinitely when transplanted into recipients treated with a synthetic peptide corresponding to residues 75-84 of (B7.75-84) in combination with a subtherapeutic dose of cyclosporine A. Furthermore, this treatment induced long-term donor-specific tolerance that was mediated by anergic cells, indicating that such peptides may have potential as therapeutics for human organ transplantation.
Superantigen-like properties of an antibody bispecific for MHC class II molecules and the V beta domain of the T cell antigen receptor.
Authors: Yagi J , Nakata M , Uchiyama T , Nishikawa M , Mizushima Y , Nishioka K , Ito K , Yagita H , Okumura K , Janeway C A 
Published: December 2022

Abstract
A working model for the action of superantigens (SAg) is that they are simple proteins having binding sites for both MHC class II molecules and the V beta domain of the TCR. Binding of a SAg to both molecules cross-links the TCR, inducing a biologic response. In this study, we have tested this working model using a SAg mimic consisting of a hybrid Ab bispecific for the murine MHC class II molecule I-E and the V beta 8 domain of the murine TCR. The bispecific Ab activates V beta 8-bearing T cells only in the presence of I-E molecules on APC when tested in vitro. The effect of the bispecific Ab in vivo revealed both clonal deletion and a reduction in the responsiveness of V beta 8-bearing T cells. Thus, the results suggest that molecules distinct from SAg that can bind to both MHC class II molecules and the V beta domain of the TCR can mimic the biologic actions of a SAg.
Monomeric homologue of mammalian CD28 is expressed on chicken T cells.
Authors: Young J R , Davison T F , Tregaskes C A , Rennie M C , Vainio O 
Published: December 2022

Abstract
A mAb recognizing a 40- to 44-kDa monomeric molecule on the surface of chicken T cells was used to screen a cDNA expression library made from Con A-stimulated chicken spleen cells. The sequence of the cDNA obtained encoded a molecule having 50% amino acid sequence identity with mammalian CD28, but the cysteine residue involved in the inter-chain bridge of the mammalian CD28 homodimer was not conserved in the chicken sequence. The molecule produced in transfected COS-7 cells was also recognized by another mAb that had previously been thought to recognize an avian homologue of CD2. The sequence data establish that this molecule is a homologue of mammalian CD28 in the strict evolutionary sense.
Lipopolysaccharide and cytokine augmentation of human monocyte IgA receptor expression and function.
Authors: Shen L , Collins J E , Schoenborn M A , Maliszewski C R 
Published: December 2022

Abstract
Receptors for IgA (Fc alpha R) are found on phagocytic cells in the peripheral blood and tissues associated with mucosal areas where IgA Abs constitute a major line of defense. Because Fc alpha R are capable of triggering protective functions of monocytes and neutrophils, such as phagocytosis and the oxidative burst, they may be important in amplifying the antimicrobial effects of IgA. Various cytokines play a role in regulating function and FcR expression of monocytes, macrophages, and neutrophils. The present studies examine the modulation of monocyte Fc alpha R by LPS and cytokines. LPS strongly up-regulated monocyte Fc alpha R expression. TNF and IL-1, produced in response to LPS, promoted Fc alpha R increase, as did GM-CSF; whereas IFN-gamma down-regulated Fc alpha R. Increased receptor expression was accompanied by augmented IgA-mediated phagocytosis. An increase in Fc alpha R-specific mRNA was detected in monocytes treated with TNF, IL-1, GM-CSF, and LPS; whereas message was reduced in cells treated with IFN-gamma. Monocyte-derived macrophages and cells of the Monomac 6 monocyte-like line expressed greater numbers of Fc alpha R than monocytes but were less responsive to LPS and TNF. Cell lines THP-1 and U937, which expressed similar or lower levels of Fc alpha R than monocytes, displayed an increase in Fc alpha R in response to LPS and, to various degrees, to TNF, IL-1, and GM-CSF. These results indicate that Fc alpha R on monocytes are modulated by endotoxin and an array of cytokines distinct from those that regulate expression of FcR for IgG.
The NF-beta A-binding element, not an overlapping NF-IL-6-binding element, is required for maximal IL-1 beta gene expression.
Authors: Buras J A , Monks B G , Fenton M J 
Published: December 2022

Abstract
NF-beta A is a monocyte, neutrophil, and B cell-specific nuclear protein that is involved in regulation of the IL-1 beta gene. These studies further define the functional role of NF-beta A in RAW264.7 monocytic cells by using transient transfection analysis. We showed that NF-beta A was able to activate transcription from a heterologous promoter in a distance-independent and dose-dependent manner. NF-beta A also appeared to function in a positionally independent manner within the IL-1 beta cap-site proximal (CSP) promoter. NF-beta A was required for maximal IL-1 beta gene expression directed by the upstream LPS-inducible enhancer element. Deletion of the NF-beta A-binding sequence resulted in an 80% reduction in basal reporter gene activity and an 86% reduction in LPS-inducible reporter gene activity in constructs containing only the enhancer and CSP promoter. Other regulatory elements located between the enhancer and the cap site were not able to substitute functionally for the absence of NF-beta A. Recently, other investigators have reported that IL-1 beta CSP promoter function was decreased by introducing multiple mutations within both the NF-beta A-binding sequence, and a putative overlapping NF-IL-6-binding sequence. We have found that these mutations predominantly affect NF-beta A binding. Furthermore NF-beta A, and not NF-IL-6, was required for supporting basal and LPS-inducible transcription from a minimal IL-1 beta CSP promoter (positions -58 to +11). This promoter region did not appear to direct monocyte-specific IL-1 beta gene expression because reporter constructs containing the IL-1 beta CSP promoter were also active in transiently transfected HeLa cells.
Functional and phenotypic change of T cells in murine acquired immune deficiency.
Authors: Kanagawa O , Gayama S , Vaupel B 
Published: December 2022

Abstract
Infection of susceptible C57BL/6 mice with defective LP-BM5 murine leukemia virus causes disease termed murine acquired immune deficiency syndrome (MAIDS). The disease is characterized by lymphoadenopathy, hyperimmunoglobulinemia, and immune deficiency in both T and B cell functions. The development of disease requires the presence of mature T cells, especially CD4 T cells, and B cells. It has previously been shown that a B cell tumor line derived from MAIDS mouse stimulated a large fraction of unprimed T cells based on TCR V beta chain expression. This stimulatory activity was assumed to be mediated by a superantigen encoded by MAIDS virus. The stimulation of T cells by viral superantigen was thought to play a role in the development of the disease. To examine the role of T cell reactivity to MAIDS superantigen, we used TCR transgenic mice. There are two distinct T cell populations which can be distinguished based on their TCR expression and function in the TCR transgenic mice, one bearing the transgene derived alpha- and beta-chain TCR that is nonreactive to MAIDS superantigen and the other bearing an endogenous alpha- but transgene-derived beta-chain TCR that is reactive to superantigen. Unlike T cells found in noninfected TCR transgenic mice, anergic T cells expanding in virally infected TCR transgenic mice are homogeneous for the TCR phenotype, indicating the presence of a selection of T cells based on their TCR expression. T cell hybridomas established by fusing T cells from virus-infected transgenic mice to thymoma cell line are also anergic. We found mRNA of defective LP-BM5 virus in a majority of T cell hybridomas from virus-infected mice but not from noninfected mice. By using in vitro infection of T cell clones with recombinant virus containing LP-BM5 MAIDS virus gag gene, we have demonstrated that virus infection directly abrogated the Ag-specific reactivity of T cells. The establishment of anergic T cell hybridomas and the in vitro infection of T cells with recombinant viruses would be a useful tool in the analysis of biochemical and molecular mechanisms of T cell dysfunction in MAIDS.
Bovine conglutinin gene exon structure reveals its evolutionary relationship to surfactant protein-D.
Authors: Liou L S , Sastry R , Hartshorn K L , Lee Y M , Okarma T B , Tauber A I , Sastry K N 
Published: December 2022

Abstract
Bovine conglutinin (BC), a member of the mammalian C-type collectin subfamily, is a serum protein synthesized in liver that is believed to play a role in natural host defense. Previously, we have characterized a full length BC cDNA and we now describe the partial characterization of a genomic clone that encodes for the BC gene (CGN1). BC is encoded by nine exons spanning &gt; 11 kb and has been localized previously to band 18 of bovine (Bos taurus) chromosome 28. Genomic sequencing demonstrated that the signal peptide/amino-terminal domain, the carbohydrate recognition domain, and the linking peptide, a domain between the collagenous region and the carbohydrate recognition domain, are each encoded by a single exon. The collagenous domain is split into five exons, with the 5' most region being located within the exon that also encodes the signal peptide/amino terminus. The remaining four collagenous domain exons are tandemly arranged with lengths of 117, 108, 108, and 117 bp, respectively. Overall, the BC genomic organization is very similar to that of the human surfactant protein-D gene, SFTP4. On the basis of identical collagen domain structures, we suggest that conglutinin and bovine surfactant protein-D evolved from a gene duplication event occurring in Bovidae after divergence from other mammals.
Antigen receptors on Thy-1+ CD3- CS-initiating cell. In vitro desensitization with hapten-amino acid or hapten-Ficoll conjugates, versus hapten-protein conjugates, suggests different antigen receptors on the immune cells that mediate the early and late components of murine contact sensitivity.
Authors: Garssen J , Van Loveren H , Kato K , Askenase P W 
Published: December 2022

Abstract
In murine contact sensitivity (CS) models, cutaneous immune responses are caused by the activity of two different Ag-specific Thy-1+ CD5+ cells. These two different cell subsets act in an obligate sequence to mediate separate early and late components of CS that are accompanied respectively by skin swelling responses at 2 and 24 h after local challenge with the hapten. The early-acting CS-initiating cells are not conventional T cells inasmuch as they are surface negative for CD4, CD8, and CD3. In contrast to this non-MHC-restricted, CS-initiating cell, the classical late-acting CS effector T cell that is recruited locally is CD3+, CD4+, CD8-, and is MHC-restricted. In our study, we have conducted experiments in which a mixture of immune CS-initiating and CS-effector cells were desensitized by incubation in vitro at 37 degrees C with various hapten-amino acid and hapten-carrier conjugates, before i.v. transfer and subsequent ear challenge of normal recipient mice. Desensitization was achieved with multivalent complexes of the relevant hapten conjugated to a variety of unrelated nonmurine carrier proteins, and, in some instances, with monovalent hapten conjugated to amino acid. Because the CS-mediating cells were desensitized in a hapten-specific manner, but these same cells transferred CS reactivity that was hapten/MHC-class II specific, it was suggested previously that these results argued in favor of a two-receptor model for T cell recognition of Ag, one receptor for hapten and the other for MHC. Our study suggests that these findings need to be reinterpreted because CS reactions are mediated by two different, Thy-1+ Ag-specific cells that act in an obligate sequence. Our data suggest that the late-acting Ag/MHC-specific CS-effector T cells are not hapten-specific. In fact, desensitization with hapten alone has a locus of action solely on the Ag receptor of the first-acting Thy-1+ CS-initiating cells--which are therefore truly hapten-specific and which are required for local recruitment of the Ag/MHC-specific late CS-effector T cells.
Modulation of fibronectin and thymic stromal cell-dependent thymocyte maturation by retinoic acid.
Authors: Meco D , Scarpa S , Napolitano M , Maroder M , Bellavia D , De Maria R , Ragano-Caracciolo M , Frati L , Modesti A , Gulino A 
Published: December 2022

Abstract
Retinoic acid (RA) controls the differentiation of a variety of cell types, although its role in influencing T cell development and the mechanisms potentially involved have not been thoroughly investigated. To study the ability of RA to modulate T cell development, we established a thymic stromal cell line (TC-1S) that supports the phenotypic maturation of CD4-8- double negative (DN) or CD3-4-8- triple negative (TN) thymocyte precursors. Cocultures of either DN or TN thymocytes on a monolayer of TC-1S cells resulted in the appearance of thymocytes with a more mature phenotype (CD4+8+ double positive, CD4+ or CD8+ single positive, and CD3(low) cells). Double negative T cell contact with TC-1S cells also increased the production of fibronectin (FN) by the thymic stroma and the expression of the VLA-4 FN receptor on the DN cells. Ab-mediated inhibition of the interaction between FN and its receptors significantly reduced the level of induced T cell maturation. Addition of RA either to TC-1S cells alone or to the coculture with DN cells decreased stromal cell FN expression, antagonized DN cell-induced increase in stromal cell FN production and significantly inhibited in vitro thymocyte maturation. The effects of RA were likely mediated by RA acid receptors alpha and gamma expressed both in DN thymocytes and TC-1S cells. Together these data suggest that FN/VLA-4 interaction may be an important component of stromal cell-dependent thymocyte phenotypic differentiation and that this interaction can be one of the targets for the influence of RA in T cell development.
Modulation of signaling via the B cell antigen receptor by CD21, the receptor for C3dg and EBV.
Authors: Luxembourg A T , Cooper N R 
Published: December 2022

Abstract
CD21 is the receptor for C3dg and EBV. Several reports have shown that these CD21 ligands, and certain anti-CD21 mAb, trigger B cell activation, particularly when combined with Ag receptor ligation. However, the characteristics, biologic functions, and importance of this CD21-signaling pathway are unknown. We have used a model we recently developed to study B cell activation induced by complex particulate Ag, such as immune complexes and viruses, to begin to examine these questions. In the current studies, we incubated purified small resting B cells with 100-nm latex beads bearing various combinations of CD21 ligands and mAbs to CD19, CD35, and the Ag receptor. CD21, CD19, and CD35 have all been implicated in modulating membrane IgM initiated signaling. Beads coated with mAb to the C3dg/EBV-binding portion of CD21, but not mAb to other portions of the CD21 molecule, triggered B cell homotypic aggregation. Beads coated with the same CD21 ligands, although inactive alone, synergized with anti-IgM mAb in greatly increasing (20- to 180-fold) mRNA levels of the c-fos nuclear proto-oncogene. Signaling via CD21 was tyrosine kinase dependent. Levels of c-myc mRNA were not altered by CD21 ligands. Anti-CD19 and anti-CD35 mAb did not augment signaling via membrane IgM as assessed by changes in c-fos mRNA levels. These findings indicate that CD21 ligands binding to the C3dg/EBV-binding site of CD21 markedly augment B cell activation initiated by Ag receptor ligation via a selective, c-fos-dependent signaling pathway.
HLA restriction and TCR usage of T lymphocytes specific for a novel candidate autoantigen, X2 MBP, in multiple sclerosis.
Authors: Voskuhl R R , Robinson E D , Segal B M , Tranquill L , Camphausen K , Albert P S , Richert J R , McFarland H F 
Published: December 2022

Abstract
Previous investigations of the major 18.5-kDa isoform of myelin basic protein (MBP) as a target autoantigen in multiple sclerosis (MS) have failed to identify an epitope uniformly recognized with higher frequency in MS patients compared with controls. Because remyelination has been observed in MS plaques, we were prompted to investigate T cells specific for myelin protein isoforms with up-regulated expression during remyelination. We have recently described such T cells that recognize the exon 2-encoded region of MBP (X2 MBP), a sequence included in the 21.5- and 20.2-kDa isoforms of MBP. These cells were shown to be CD4+, HLA class II restricted, and cytolytic. In members of one multiplex MS family, X2 MBP-specific T lymphocytes were as prevalent as T cells specific for immunodominant regions within the major 18.5-kDa isoform of MBP. The present study characterizes X2 MBP-specific T cell responses in additional multiplex MS family members as well as in heterogeneous (non-familial) MS patients and in healthy controls. The frequencies of X2 MBP-specific T cells in each of the affected family members from two of three MS families were significantly increased as compared with both the heterogeneous MS group and the healthy control group. Also, X2 MBP-specific T cell lines from affected family members were primarily restricted to molecules encoded by the DR2/DQw1 allele. Although TCR usage was generally heterogeneous, there was evidence of intraindividual sequence identity. These data suggest that: 1) Myelin proteins with up-regulated expression during the course of disease should be considered as candidate autoantigens in MS. 2) The functional basis for the association of DR2/DQw1 inheritance with MS susceptibility may be related to presentation of autoantigens by this allele. 3) TCR therapy will need to be individually tailored to target the most prevalent autoantigen-specific response.