SEARCH · PubMed Health

Results for “Class”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources

PubMed1989

Tolerance induction of allo-class I H-2 antigen-reactive Lyt-2+ helper T cells and prolonged survival of the corresponding class I H-2-disparate skin graft.

C57BL/6 (B6) mice were i.v. presensitized with class I H-2-disparate B6-C-H-2bm1 (bm1) spleen cells. Such presensitization resulted in almost complete abrogation of bm1-specific Lyt-2+ T cell-mediated proliferative and IL-2-producing capacities as measured by MLC of lymphoid cells from presensitized B6 mice with stimulating bm1 cells. In contrast, comparable magnitude of CTL responses was generated in bulk cultures from presensitized B6 lymphoid cells to that obtained in unpresensitized B6 responding cultures. These differential influences of Lyt-2+ T cell functions were also demonstrated by limiting dilution assays; frequencies of proliferative and IL-2-producing T cell precursors were as low as undetectable in presensitized B6 lymphoid cells, whereas an appreciable frequency of CTL precursors in a portion of the same lymphoid cells was observed. When bm1 skin grafting was performed in B6 mice i.v. presensitized with bm1 cells, the strikingly prolonged survival of bm1 skin grafts was observed. It was also demonstrated that the bm1 skin graft-bearing B6 mice which had been presensitized with bm1 cells not only exhibited a continuing suppressive state of bm1-specific helper (proliferative and IL-2-producing) function but also failed to generate anti-bm1 CTL responses. These results indicate that 1) i.v. presensitization with class I H-2 alloantigens results in selective tolerance of Lyt-2+ Th cells which is adequate for inducing prolonged graft survival, 2) the induction of complete abrogation of CTL potential is not absolute requirement for the prolongation of graft survival, and 3) residual CTL potential is attenuated after grafting so far as Th cells are rendered tolerant.

Animals↗

PubMed1989

Class III aldehyde dehydrogenase from rat liver: super-family relationship to classes I and II and functional interpretations.

In summary, evidence of the relatedness of the Class I/II A1DHs of human and horse liver and the Class III A1DH of rat liver is seen at the primary, predicted secondary, and gene structural levels. The primary structural relationships support the functional significance of some (but not all) specific amino acid residues previously indicated by other studies.

Aldehyde Dehydrogenase↗

PubMed1987

The two classes of objects and the two classes of transference.

The problem of reconciling within a single comprehensive theory and model the various phenomena of object love and narcissistic love is reviewed. This problem has given rise to such unintegrated theories as those of object-relations on the one hand and of drive-discharge and conflict on the other. Following an early suggestion of Freud a distinction is made between two different classes of objects: the discharge object and the reflexive object. Their distinctive lines and stages of development are described, each one being comprehended within the systems (structural) model of psychic organization. The development of the discharge object follows the differentiation of the ego out of the ego-id matrix while that of the reflexive object follows the development of the ego ideal-superego complex through processes of introjection. Accordingly, two classes of transference are then distinguished, the discharge transference and the reflexive transference. Their essential developmental and clinical differences are discussed.

Arousal↗

PubMed1993

Effect of tunicamycin treatment on ligand binding to the erythropoietin receptor: conversion from two classes of binding sites to a single class.

Scatchard analyses of erythropoietin (EPO) binding to its receptor (EPO-R) have shown that some erythroid cells display a biphasic nature of the ligand-saturation curve, indicating the presence of two classes of binding sites with different affinities. The biochemical basis accounting for this observation is unknown. We found that the culture of a human erythroleukemia cell line with tunicamycin, an inhibitor of N-glycosylation, converted the biphasic Scatchard plot to a single phase with high-affinity sites. Scatchard plots of baby hamster kidney (BHK) cells that had been engineered to express cloned mouse EPO-R were also biphasic and the plots of cells cultured with tunicamycin became a single phase with high-affinity sites. Mouse EPO-R is glycosylated at one asparagine residue in the extracellular region. The mutant EPO-R, in which asparagine residue responsible for N-glycosylation was replaced with glutamine residue, was expressed on BHK cells. Unexpectedly, mutant EPO-R was similar in ligand binding to wild-type EPO-R. BHK cells that expressed mutant EPO-R showed biphasic Scatchard plots that were converted to single-phase plots with only high-affinity sites by tunicamycin treatment. These results indicate that the N-linked sugar of EPO-R is not involved in the manifestation of two classes of binding sites, and that there is a yet unidentified glycoprotein crucial for the ligand-saturation characteristics of EPO-R.

Amino Acid Sequence↗

PubMed1977

Mediation of macrophage cytolytic and phagocytic activities by antibodies of different classes and class-specific Fc-receptors.

The classes of antibodies that mediate the phagocytosis and cytolysis of 51Cr-labeled chicken erythrocytes by IC-21 macrophages, an established line of mouse peritoneal macrophages, were identified. The phagocytic activity of IC-21 macrophages, as determined by a functional inhibition assay with mouse myeloma proteins, depended mainly on IgM and IgG2a antibodies and to a lesser extent on IgG2b antibodies. Extracellular cytolysis of target cells was mediated solely by IgG2b antibodies. These results correlate with the previously documented specificities of discrete Fc-receptors for IgG2a and IgG2b immunoglobulins on IC-21 cells. Thus, phagocytosis and cytolysis appear to be mediated by antibodies of different classes operating through separate and distinct sites on the surface of IC-21 macrophages.

Antibody Specificity↗

PubMed1997

V alpha 3.2 selection in MHC class I mutant mice: evidence for an alternate orientation of TCR-MHC class I interaction.

TCR V alpha elements are expressed preferentially in CD4 or CD8 subsets in a manner that is largely independent of MHC haplotype. It is likely that the V alphas interact preferentially with conserved regions of class I or class II molecules. To investigate the topology of binding of TCR to MHC-peptide complexes, we screened a panel of H-2Kbm mutants for differential V alpha expression. One strain, bm23, showed a consistent alteration in V alpha expression, with increased V alpha 3.2 expression in CD8 peripheral T cells. This overselection is manifest in CD8 single-positive thymocytes and appears to be due to enhanced positive selection on Kbm23. There is no apparent effect of V beta elements. The Kbm23 molecule is unique compared with Kb and the other Kbm molecules at residue 75 on the helix of the alpha 1 domain, suggesting an interaction between V alpha 3.2 and the alpha 1 helix at this point. Such an interaction is inconsistent with the orientation of TCR and MHC defined in two crystal structures, but is consistent with an orientation where the TCR is rotated by 180 degrees relative to MHC.

Animals↗

PubMed1997

Cellular levels of class 1 and class 3 aldehyde dehydrogenases and certain other drug-metabolizing enzymes in human breast malignancies.

Molecular determinants of cellular sensitivity to cyclophosphamide, long the mainstay of chemotherapeutic regimens used to treat metastatic breast cancer, include class 1 and class 3 aldehyde dehydrogenases (ALDH-1 and ALDH-3, respectively), which catalyze the detoxification of this agent. Thus, interindividual variation in the activity of either of these enzymes in breast cancers could contribute to the wide variation in clinical responses that are obtained when such regimens are used to treat these malignancies. Consistent with this notion, ALDH-1 levels in primary and metastatic breast malignancies were found to range from 1-276 and 8-160 mIU/g tissue, respectively, and those of ALDH-3 range from 1-242 and 6-97 mIU/g tissue, respectively. ALDH-1 and ALDH-3 levels in normal breast tissue predicted the levels of these enzymes in primary and metastatic breast malignancies present in the same individuals. Confirming and extending the observations of others, levels of glutathione, a molecular determinant of cellular sensitivity to various DNA cross-linking agents including cyclophosphamide, and of DT-diaphorase, glutathione S-transferases, and cytochrome P450 1A1, each of which is known to catalyze the detoxification/toxification of one or more anticancer agents (although not of cyclophosphamide), also varied widely in primary and metastatic breast malignancies. Given the wide range of ALDH-1, ALDH-3, and glutathione levels that were observed in malignant breast tissues, measurement of their levels in normal breast tissue and/or primary breast malignancies prior to the initiation of chemotherapy is likely to be of value in predicting the therapeutic potential, or lack thereof, of cyclophosphamide in the treatment of metastatic breast cancer, thus providing a rational basis for the design of individualized therapeutic regimens when treating this disease.

Adult↗

PubMed1995

CD8+ type 1 CD44hi CD45 RBlo T lymphocytes control intracellular Brucella abortus infection as demonstrated in major histocompatibility complex class I- and class II-deficient mice.

Genetically engineered mice with a targeted disruption in the beta 2-microglobulin (beta 2-m) gene or the H2-I-A beta chain (A beta) which lack functional CD8+ or CD4+ T cells, respectively, were used to assess the role of T cell subsets in Brucella abortus infection. Murine brucellosis was markedly exacerbated in beta 2-m-deficient mice (beta 2-m-/-) compared to A beta mutant (A beta-/-) or C57BL/6 mice, strongly indicating that optimal resistance to B. abortus requires CD8+ T cells. Splenocytes from Brucella-primed beta 2-m-/-, A beta-/- and C57BL/6 mice exhibited a type 1 cytokine profile marked by elevated IFN-gamma mRNA expression and protein production, and basal levels of IL-2 and IL-4 transcripts. B. abortus did not induce secretion of TGF-beta 1, but substantial IL-10 activity was detected in spleen cell supernatants from all mouse strains studied. CD8+ T cells from A beta-/- and C57BL/6 mice displayed a CD44hi CD45RBlo phenotype and a type 1 cytokine transcription profile featuring high levels of IFN-gamma mRNA. Additionally, we have shown the ability of C57BL/6 CD8+ CTL to kill Brucella-infected macrophages. This study illustrates the predominant role of MHC class I-restricted T cells in controlling B. abortus infection.

Animals↗

PubMed2000

HLA class I and class II profiles of patients presenting with Sydenham's chorea.

Sydenham's chorea (SC) may occur in rheumatic fever (RF) patients without arthritis and carditis. In this study we typed HLA antigens and alleles in patients presenting with the distinct major clinical manifestations of RF, i.e., chorea, carditis, or arthritis, in population and family studies. We evaluated 91 patients with RF for HLA-A, HLA-B, and HLA-DR antigens; of these, 33 had pure chorea, 26 pure carditis, 16 pure arthritis, and 16 carditis plus arthritis. We also typed 24 SC patients and their unaffected siblings for HLA-DRB1 and HLA-DQB1 alleles using molecular methods. HLA-B49 and HLA-DR1 antigens were overrepresented in the total group of patients with RF and in all the subgroups studied, excluding the SC subgroup in which the frequency of HLA-DR1 antigen was not increased. The frequencies of the HLA-DRB1 and HLA-DQB1 alleles in patients with pure chorea were not significantly different from those observed in controls. Similarly, the frequencies of HLA class II alleles in SC patients did not differ significantly from those observed in unaffected siblings. These findings show that immunogenetic susceptibility to RF varies according to the major clinical manifestation presented by the patient.

Adolescent↗

PubMed1990

Organization of human FcRII and FcRII-like (beta FcRII) genes: structural homology to HLA class I and class II genes.

Genomic EMBL 3 DNA clones representing part of the human Fc gamma receptor II and the beta Fc gamma receptor II genes were characterized. One of them contains the first five exons including the 5' flanking region of the beta FcRII gene. The signal peptide, the extracellular domains, the putative membrane spanning region, and the first amino acids of the cytoplasmic region encoded by these five exons are spread over approximately 11 kb. Another genomic DNA clone comprises four exons encoding the second extracellular domain and the transmembrane and cytoplasmic regions of the FcRII. Alignment of the genomic DNA clones reveals that these FcR genes are identically organized. Comparison of the corresponding regions of these clones shows that not only the exons are strikingly homologous but also the splice junctions and parts of the intervening sequences are conserved. Furthermore, the genomic organization of FcRII and HLA-class I resemble each other.

Antigens, Differentiation↗

PubMed1993

Host T-cell primary allosensitization to MHC class-I- and class-II-expressing human cardiac myocytes requires the presence of a second signal.

Normal FHCMs, or transformed cell lines derived from FHCMs, such as W1, even after induction of MHC antigens by pretreatment with IFN-gamma, failed to induce proliferation of allogeneic human PBMCs in vitro. To test the hypothesis that antigen-specific T-cell activation and proliferation require not only the binding of the TCR with its ligand, the MHC molecule, but also a second signal that involves the interaction of T-cell surface molecules with their natural ligands on the stimulating cells, a mAb against CD28 was used. Cocultures of allogeneic PBMCs with IFN-gamma-pretreated irradiated FHCMs or the W1 cell line in microtiter plates containing immobilized anti-CD28 mAb induced marked stimulator cells MHC class-II-specific proliferative responses. The W1 cell line and FHCMs failed to express detectable levels of the BB1/B7 molecule (the natural ligand for CD28) as determined by flow microfluorometry or mRNA levels coding for BB1/B7 as determined by RT-PCR. These data suggest that one of the probably reasons for the failure of MHC-expressing cardiac myocytes to induce allogeneic activation is the absence of costimulatory signals.

Base Sequence↗

PubMed2004

Short peptide sequences containing MHC class I and/or class II epitopes linked to nano-beads induce strong immunity and inhibition of growth of antigen-specific tumour challenge in mice.

Peptide based vaccines offer practical advantages, but unmodified peptides usually require an adjuvant or delivery vehicle to promote immunogenicity. When peptides containing ovalbumin (OVA) derived CD4 and CD8 T cell epitopes were conjugated to 0.05 microm nano-beads, they gave strong immune responses and inhibition of growth of tumour cells expressing the CD8 T cell epitope with MHC class I. These responses were inducible with both high (50 microg) and low (5 microg) peptide doses after a single immunisation. The helper CD4 T cell epitope was unnecessary for induction of CD8 T cell or tumour challenge responses. However, the CD4 T cell epitope contained a B cell epitope and triggered strong antibody responses. This simple approach offers a convenient experimental tool and a potentially useful clinical method for peptide immunisation.

Animals↗

PubMed1997

A sensitive fluorometric assay for quantitatively measuring specific peptide binding to HLA class I and class II molecules.

A sensitive, highly reproducible assay was developed for measuring binding of peptides to various HLA class I and II alleles. The assay is based on competition for binding to HLA between a peptide of interest and a fluorescent labelled standard peptide. This mixture is incubated with HLA to obtain equilibrium binding, and subsequently separated on an HPLC size-exclusion column in (i) a protein fraction containing HLA and bound peptide and (ii) a free peptide fraction. Each assay uses only 100 fmol labelled peptide and approximately 10 pmol of HLA. The analytical system contains an autosampler that samples from 96-well microtiter plates. Injections and data recording/evaluation is fully automated. Typical analysis time is 10-12 min per sample. The fluorescence in the HLA-bound peptide and free peptide containing fractions is measured on-line. The ratios of fluorescence signal in protein and peptide fractions at various concentrations of the peptide of interest are determined. IC50 values are calculated from the binding curve as obtained by curve fitting of the data. Here we show results for peptide binding to HLA-DR1 and -DR17 molecules purified from detergent solubilized cell lysates. and for recombinant HLA-A*0201 and HLA-A*0301 expressed in E. coli. The assay reported is sensitive and reproducible. It is non-radioactive and is non-labor intensive due to the high degree of automation.

Amino Acid Sequence↗

PubMed1998

Analysis of HLA class I and class II in Na-Dene and Amerindian populations from British Columbia, Canada.

We analyzed the distribution of HLA class II alleles and haplotypes in one Na-Dene (Athabaskan) group from British Columbia (Canada) by PCR amplification of the DRB1, DQA1 and DQB1 second exon sequences. We extended the typing of the DRB1 in an Amerindian group (Penutian) from British Columbia. The presence of the alleles DRB1* 0405, *0407 and *0410 only in Na-Dene and alleles DRB1*0408, *1301*1302, *1304, *1305, *1502 and *1601 only in Amerindians suggests separate origins of these two groups. There were fifteen different DRB1/DQA1/DQB1 haplotypes. One unique haplotype previously reported in Native Americans was found. Thirty-four per cent of Athabaskans presented Native American haplotype DRB1*1402/DQA1*0501/DQB1*0301. In addition, the results of this study are compatible with previous evidence with mitochondrial (mtDNA) polymorphisms indicating that Amerindians and Na-Dene populations derived from different migrations from Asia.

Alleles↗

PubMed2000

Crystal structure of Urtica dioica agglutinin, a superantigen presented by MHC molecules of class I and class II.

BACKGROUND: Urtica dioica agglutinin (UDA), a monomeric lectin extracted from stinging nettle rhizomes, is specific for saccharides containing N-acetylglucosamine (GlcNAc). The lectin behaves as a superantigen for murine T cells, inducing the exclusive proliferation of Vbeta8.3(+) lymphocytes. UDA is unique among known T cell superantigens because it can be presented by major histocompatibility complex (MHC) molecules of both class I and II. RESULTS: The crystal structure of UDA has been determined in the ligand-free state, and in complex with tri-acetylchitotriose and tetra-acetylchitotetraose at 1.66 A, 1.90 A and 1.40 A resolution, respectively. UDA comprises two hevein-like domains, each with a saccharide-binding site. A serine and three aromatic residues at each site form the principal contacts with the ligand. The N-terminal domain binding site can centre on any residue of a chito-oligosaccharide, whereas that of the C-terminal domain is specific for residues at the nonreducing terminus of the ligand. We have shown previously that oligomers of GlcNAc inhibit the superantigenic activity of UDA and that the lectin binds to glycans on the MHC molecule. We show that UDA also binds to glycans on the T cell receptor (TCR). CONCLUSIONS: The presence of two saccharide-binding sites observed in the structure of UDA suggests that its superantigenic properties arise from the simultaneous fixation of glycans on the TCR and MHC molecules of the T cell and antigen-presenting cell, respectively. The well defined spacing between the two binding sites of UDA is probably a key factor in determining the specificity for Vbeta8.3(+) lymphocytes.

Amino Acid Sequence↗

PubMed2003

Alpha1 and alpha2 domains of Aotus MHC class I and Catarrhini MHC class Ia share similar characteristics.

Functional and structural analyses of major histocompatibility complex (MHC) class I molecules of the Aotus genus are necessary to validate it as a solid animal model for biomedical research. We thus isolated, cloned and sequenced exons 2 and 3 from three Aotus species (A. nancymaae, A. nigriceps and A. vociferans). We found 24 sequences, which divided into two different groups (Ao-g1 and Ao-g2). A further sequence was identified as a processed pseudogene (Aona-PS2). Both sequence evolution and variability analyses showed that Ao-g1 and Ao-g2 display similar characteristics to Catarrhini's classical loci, such as positive selection pressure at the peptide binding region (PBR) high variability and a trans-specific evolution pattern.

Amino Acid Sequence↗

PubMed1992

Class I and Class III malocclusion sub-groupings related to headform type.

Different headform types establish different lines of craniofacial growth resulting in anatomic sub-groupings of Classes I, II, and III with characteristic morphologic features. Several key basicranial and facial relationships are involved, with the nasal region particularly significant in group distinctions.

Adolescent↗

PubMed1990

Cytotoxic T cell recognition of an endogenous class I HLA peptide presented by a class II HLA molecule.

Human leukocytes were stimulated in vitro with peptides corresponding in sequence to the highly variable helix of the alpha 1 domain of various HLA-B and -C molecules. A CD4+ CD8- cytotoxic T cell line, CTL-AV, that is specific for the HLA-B7 peptide presented by HLA-DR11.1 was obtained. The HLA-DR11.2 molecule, which only differs at three residues from HLA-DR11.1, did not present the HLA-B7 peptide to CTL-AV. Peptides from the alpha 1 domain helix of other HLA-A and HLA-B molecules, but not HLA-C molecules, competed with the HLA-B7 peptide for binding to HLA-DR11.1. A cell line (WT50) that coexpresses HLA-B7 and HLA-DR11.1 was killed by CTL-AV in the absence of any added HLA-B7 peptide. The processing and presentation of HLA-B7 in these cells appears to be through the endogenous, and not the exogenous, pathway of antigen presentation. Thus, Brefeldin A inhibits presentation and chloroquine does not. Furthermore, introduction of purified HLA-B7 molecules into HLA-DR11.1+, HLA-B7- cells by cytoplasmic loading via osmotic lysis of pinosomes, but not by simple incubation, rendered them susceptible to CTL-AV killing. These results provide an example of class II major histocompatibility complex (MHC) presentation of a constitutively synthesized self protein that uses the endogenous pathway of antigen presentation. They also emphasize the capacity for presentation of MHC peptides by MHC molecules.

Anti-Bacterial Agents↗