Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The murine T cell surface molecules Ly-6C and Thy-1 are genetically and structurally distinct, yet they share two interesting properties: both are attached to the plasma membrane through a glycophosphatidylinositol linkage, and some mAb reactive with these molecules can activate T cells. Although mAb for Ly-6C and Thy-1 appear to mimic the function of physiologic ligands, direct evidence for the existence of these putative ligands has not been presented. In this report, we describe CTL clones that use Ly-6C and Thy-1 as accessory molecules for activation of cytolysis and the production of IFN-gamma based on inhibition of these functions with mAb. These studies were facilitated by the derivation of a nonactivating hamster IgM mAb specific for Ly-6C. CTL clones that use Ly-6C and Thy-1 as accessory molecules include a subpopulation of the previously described CD8+ alloreactive CTL that are not inhibited by mAb reactive with CD8, a CD8+ TCR-alpha/beta+ T cell clone specific for HSV glycoprotein D, and a CD4-CD8- TCR-gamma/delta+ T cell clone specific for HSV glycoprotein I. The role of Ly-6C and Thy-1 in target cell recognition is to some degree tissue-specific with respect to the APC/target cell. A mAb specific for Ly-6C appears to inhibit activation by prevention of adhesion between the effector cells and the target cells. This is the most direct evidence to date of a functional ligand for Ly-6C.
 ...
PMID:Accessory molecules involved in antigen-mediated cytolysis and lymphokine production by cytotoxic T lymphocyte subsets. I. Identification of functions for the T cell surface molecules Ly-6C and Thy-1. 810 17

Increasing evidence indicates that nerve growth factor (NGF), in addition to its neurotrophic actions, exerts specific effects on cells of the immune system. This report show that the CD4-positive T cell line 9/6 expresses trk protooncogene, the signal transducing receptor unit for NGF, after TCR-mediated activation by Ag and APC. This receptor is of functional importance because interaction of NGF with Ag-stimulated 9/6 T cells induced the transcriptional activation of the c-fos gene, a hallmark of the biochemical response to NGF. Our findings that neither mitogen nor Ag stimulation induced the expression of the low affinity NGF receptor in 9/6 T cells indicate that trk alone is sufficient to mediate biologic activity of NGF in T lymphocytes.
 ...
PMID:Expression of functional trk tyrosine kinase receptors after T cell activation. 814 77

APC use class II molecules of the MHC to present peptide Ag to Th cells. Interaction of the TCR and CD4 with the class II-peptide complex, together with co-stimulatory signals provided by the APC, activates the T cell. B lymphocytes express class II molecules and can also be induced to express co-stimulatory molecules, allowing them to act as APC to Th cells. In addition to T cell activation, class II binding by T cells has been shown to result in the transmission of signals to B cells. Signal transduction via MHC class II has been well documented in B cells of both mice and humans and is implicated in the processes of cellular adhesion, Ag presentation, and Ag-dependent B cell activation. The regions of the class II MHC molecule which are involved in signal transduction to the B cell are not clearly defined. However, previous studies have suggested that the beta chain of the alpha beta heterodimer has a predominant role in B cell signaling. To examine the role of the cytoplasmic domain of this molecule in class II-mediated signaling to a mouse B cell clone, we have prepared and analyzed a set of subclones expressing sequentially truncated forms of A beta b. Our results demonstrate that only the 8 membrane-proximal amino acids of the cytoplasmic domain are required for signaling. However, specific conserved amino acids within this minimal length are required for successful signal transduction; length alone is not sufficient. Examination of the signaling ability of these truncated beta chains suggests that conserved residues at positions 227 and 228 of the cytoplasmic domain may have particularly important effects on signal transduction. A beta b chains from which the entire cytoplasmic domain have been removed are still capable of transmitting a detectable, although reduced, signal to B cells. Thus, the transmembrane and/or extracellular domains may also be involved in the signaling process.
 ...
PMID:Length and sequence requirements of the cytoplasmic domain of the A beta molecule for class II-mediated B cell signaling. 822 24

Our recent study indicated that all the insulin autoimmune syndrome (IAS) patients had specific HLA class II alleles, the DRB1*0406, DQA1*0301, and DQB1*0302, which allowed T cells to proliferate when autologous APC were exposed to human insulin. The study implied that gene products of DRB1*0406, DQA1*0301, and/or DQB1*0302 may be involved in the presentation of human insulin to T cells. We therefore examined T cell response of healthy donors with different HLA phenotypes to human insulin using an autologous MLR system. The T cells from not only IAS patients but also healthy donors were able to proliferate after exposure of human insulin to autologous APC with DRB1*0406, DQA1*0301, and DQB1*0302 products. The class II molecules are considered to be involved in the recognition of human insulin by T cells. The proliferative response of T cells was completely blocked by anti-HLA-DR mAb and not by anti-HLA-DQ mAb or other mAb. Furthermore, human insulin-specific CD4-positive T cell clones were established from blast cells in autologous MLR of PBMC from two healthy donors with DRB1*0406 in the presence of human insulin. Using DRB1*0406-transfected L cells as APC, we confirmed that these T cells clones recognize human insulin in the context of gene products of DRB1*0406. These results provide the first evidence that HLA-DRB1*0406 products act as the dominant restriction element for the presentation of human insulin to T cells, and suggest that this particular class II gene, HLA-DRB1*0406, contributes to the development of IAS.
 ...
PMID:Recognition of human insulin in the context of HLA-DRB1*0406 products by T cells of insulin autoimmune syndrome patients and healthy donors. 822 61

Epidermal Langerhans cells (LC) are a unique subtype of I-A+ dendritic cells able to present Ag for CD4-dependent immune responses. To investigate whether cutaneous Ag presentation is regulated by thymic elements or soluble factors produced by thymus-derived cells, we compared LC function in athymic nude mice and euthymic normal controls. Examination of the ability of LC to present alloantigens to T cell-enriched responder populations, and insulin to an insulin-specific T cell hybridoma, demonstrated that this function is deficient in LC from inbred and outbred strains of congenitally athymic (nu/nu) mice compared with euthymic litter mates. Adoptive transfer of thymic tissue from euthymic to athymic mice reconstituted the ability of LC derived from athymic mice to present alloantigens. To investigate whether an altered local cytokine microenvironment was responsible for the diminished LC function in athymic mice, various cytokines were administered in vivo and in vitro before determination of alloantigen presentation by epidermal cells from athymic and euthymic mice. Continuous intraperitoneal infusion of granulocyte-macrophage colony stimulating factor (GM-CSF) or TNF-alpha, but not IL-1 alpha or IL-2, restored alloantigen presenting ability in athymic LC. In vitro preincubation of LC in GM-CSF or TNF-alpha but not in other cytokines tested also reconstituted alloantigen presentation by LC from athymic mice in most, but not all, of the experiments performed. Furthermore, analysis of cytokine production by epidermal cells in athymic and euthymic mice revealed that epidermal cells from athymic mice produce less GM-CSF and more TNF-alpha, but normal amounts of various other cytokines. However, reconstitution of athymic mice with thymic tissue did not result in normalization of GM-CSF or TNF-alpha production by epidermal cells. These data suggest that LC Ag presenting ability is regulated by thymic factors and that adequate function of cutaneous APC in situ may require the continuous presence of sufficient amounts of cytokines including GM-CSF and TNF-alpha.
 ...
PMID:Deficient antigen presentation by Langerhans cells from athymic (nu/nu) mice. Restoration with thymic transplantation or administration of cytokines. 837 84

Immunoconjugates composed of avidin linked to biotinylated antibodies specific for different surface determinants on cells of the immune system were evaluated for their ability to induce adjuvant-independent anti-avidin IgG responses in mice. Previously, we demonstrated that allele-specific murine anti-class II MHC-avidin immunoconjugates were immunogenic in mice bearing the appropriate haplotype. Herein we report the immunotargeting potential of heterologous anti-class II MHC antibodies specific for framework determinants, and extend the range of effective targets to include certain non-MHC structures present on APC (e.g., 33D1 on dendritic cells, 14.8 on B cells, and CD45--the leukocyte common antigen). However, antibodies with other specificities (e.g., leukocyte integrins and some macrophage markers) were not effective targeting vehicles. Surprisingly, immunoconjugates specific for CD3 and CD4 were immunogenic. The isotype distribution of the anti-avidin antibody response induced in mice by immunotargeting to class II MHC or 33D1 was similar to that induced by immunization with Ag emulsified in complete Freund's adjuvant. Most of the antibody induced was IgG1 (65-75%), but a significant proportion was IgG2a (20-30%). We also demonstrate that immunotargeting is able to prime for long-term immunologic memory in mice.
 ...
PMID:Studies of the adjuvant-independent antibody response to immunotargeting. Target structure dependence, isotype distribution, and induction of long term memory. 837 92

The initial event triggering the activation of Th cells occurs when the TCR interacts with antigenic peptide in the context of the MHC II on APC. Various T cell accessory molecules including CD4, CD28, and LFA-1 participate and facilitate the activation event. Although some evidence for the interaction of MHC II and CD4 is available, the site of MHC class II (alpha-chain, beta-chain, or both chains) for CD4 interaction has not yet been clearly defined. Results from different laboratories had indicated the involvement of alpha 1, beta 1, and beta 2 domains of MHC class II molecules in CD4 interaction. Recently, a conserved site of DR beta 2 domain has been identified that involves CD4 interaction that is analogous to MHC class I binding site for CD8 molecule. In this report, direct binding of affinity-purified HLA-DR2 dimer and its isolated alpha- and beta-chains to CD4 was studied using a CD4-transfected HeLa cell line. Preferential binding of the beta-chain and intact MHC II dimer to the CD4-transfected cells was observed and found to be specifically inhibited by anti-CD4 mAb. In contrast, the isolated alpha-chain of HLA DR2 did not show significant binding to CD4-transfected cells. Complexes of radiolabeled DR2 dimer or beta-chain alone with an immunodominant epitope from myelin basic protein (83-102) did not show any further increase in binding of these molecules. Binding of the beta-chain to CD4+ cells was markedly inhibited by a DR beta 1 peptide (35-46) and was partially inhibited by a DR beta 2 peptide (134-148) of MHC class II molecule. These results suggest the involvement of at least two conserved regions of the beta polypeptide chain of MHC class II in CD4 interaction. Because in our experiments transfected cells lack TCR molecules and the binding of DR2 to the CD4-transfected cells was unaffected by added antigenic peptide, it is possible that the interaction of MHC class II to CD4 is independent of TCR occupancy.
 ...
PMID:Purified beta-chain of MHC class II binds to CD4 molecules on transfected HeLa cells. 843 82

10BK.1 T clone cells of (B10 x B10.BR)F1 genotype specifically react to peptides of OVA, frequently encountered in OVA preparations, and to the synthetic peptide OVA257-264 in an H-2Kb-restricted manner; the T clone cells produce lymphokines and proliferate in the absence of added APC, suggesting self-presentation of the Ag by the T cells. In accordance with their CD8+ CD4- phenotype 10BK.1 cells exhibit cytotoxic capacity. When the target cells were pretreated with OVA257-264 only cells bearing H-2Kb molecules were lysed. However, when the relevant OVA peptide was present during the 4-h 51Cr release assay 10BK.1 cells lysed target cells expressing H-2Kb molecules as well as target cells lacking H-2Kb elements. Likewise, 10BK.1 cells pretreated with OVA257-264 for 1 h and washed extensively to remove residual Ag were able to kill syngeneic and allogeneic target cells. Killing of allogeneic targets in the presence of Ag was inhibited by antibodies directed at H-2Kb. Allogeneic target cells were not killed when 10BK.1 cells were stimulated by peptide-pulsed syngeneic cells. Triggering of the TCR/CD3 complex of 10BK.1 cells was involved during the activation phase but not during the lytic phase. IL-2 did not participate in the MHC-unrestricted killing event. To explain the observed MHC-unrestricted cytotoxicity of 10BK.1 cells, the following model is proposed. In an initial step 10BK.1 cells present the relevant OVA peptide to one another in a H-2Kb-restricted fashion. The cells are thereby triggered to mobilize the lytic machinery. In a second step sensitized 10BK.1 cells lyse allogeneic target cells. Thus, the MHC-unrestricted cytotoxicity can be dissected into an MHC-restricted phase of 10BK.1 cell activation and an MHC-unrestricted lytic phase. Cytotoxic T cells with Ag self-presentation functions may account for tissue damage during bacterial infections.
 ...
PMID:Manifestation of the MHC-unrestricted killing potential of a cytotoxic T cell clone requires activation in response to MHC-restricted self-presentation of antigen. 845 44

T cell responses to the variant surface glycoprotein (VSG) previously have not been detected in animals infected with the African trypanosomes despite the fact that such animals make strong T-dependent B cell responses to VSG molecules displayed by the parasites. In the present study, we have examined B 10.BR mice for VSG-specific Th cell responses at different times after infection with Trypanosoma brucei rhodesiense clone LouTat 1. T cell populations derived from different tissues were tested for their ability to proliferate and secrete cytokines when stimulated with purified LouTat 1 VSG. Furthermore, VSG-specific T cell lines and clones were derived from immunized mice and examined for their phenotypic and functional profiles in comparison with T cell responses of infected mice. The results of this study show that VSG-specific T cells were not consistently detected in the peripheral lymphoid tissues such as spleen or lymph nodes of infected animals. In contrast, VSG Ag-specific T cells were detectable principally in the peritoneal T cell populations of infected mice. Peritoneal T cells did not proliferate in response to VSG, yet produced substantial cytokine responses when stimulated; the cytokines produced were IFN-gamma and IL-2, without detectable IL-4. The cellular phenotype of VSG-responsive T cells was that of classical Th cells in that all cells were CD4-positive and expressed the CD3 alpha/beta TCR membrane complex. Thus, the VSG appears to preferentially stimulate a Th1 cell subset response during infection. Intrinsic molecular characteristics of the VSG molecule did not induce mice to make this response, however, since VSG-specific T cell lines derived from VSG-immunized mice displayed cytokine profiles characteristic of both Th1 and Th2 cells. Isolation of Th1 clones from selected lines demonstrated that these cells displayed the same membrane-phenotypic characteristics and cytokine profiles as the T cells from infected mice. Furthermore, all Th clones were VSG type-specific, APC-dependent, and I-Ak-restricted in their responses. In summary, these experiments provide the first direct evidence for VSG-specific responses at the T cell level. T cell responses to the VSG molecule during infection appear to be anatomically compartmentalized and exhibit evidence of clonal maturation (cytokine production) but not clonal expansion (proliferation) after antigenic stimulation. The cellular phenotype and cytokine profiles predict that infection predisposes the animals to mount Th1 cell subset responses to VSG. The results of this study, including the T clones generated, provide an experimental basis for examining the regulation of VSG-specific immune responses during infection.
 ...
PMID:Characterization of T helper cell responses to the trypanosome variant surface glycoprotein. 845 63

Dendritic cells (DC) have been isolated from blood, lymphoid tissue, and other tissues, as potential members of a hemopoietic lineage of specialist APC for naive T lymphocyte activation. To define human bone marrow (BM) DC we have attempted to identify allostimulatory cells with DC-like characteristics among human BM mononuclear cells (BMMC) by FACS cell sorting and immunophenotyping, monitoring the APC function of different cell lineages in the human primary MLR. We show that fresh human BM stimulates allogeneic T lymphocytes with an activity equal to or greater than that of peripheral blood. As with DC from other tissue sources, the most potent stimulatory activity was found in the low density BMMC, and these cells, like peripheral blood, stimulated a maximal allogeneic MLR response at days 5 to 6. FACS purification of the allostimulatory population in fresh human BMMC was undertaken by using a wide range of mAb directed against lineage-associated molecules of mature and immature lymphoid, erythroid, and myeloid cells. The most potent constitutive BMMC stimulatory activity was located in the CD3-, CD11b-, CD14-, CD15-, CD16-, CD19-, CD57-, and glycophorin A- population. A mixture of antibodies to these Ag was used to isolate a "mix-negative" BMMC population, which contained the most highly potent MLR-stimulatory cells. Further cytologic and immunophenotypic analysis of this population revealed an enriched population of HLA-DP+, HLA-DQ+, HLA-DR+, and CD45+ cells, with morphologic similarities to the human tonsil and blood DC. These cells were CD4- and CD1a- and were weakly CD33+ (but CD15-), suggesting a possible early myeloid origin distinct from both the committed granulocytic and monocytic lineages. In addition, they lacked both CD10 and CD20, making a lymphoid origin unlikely. Further identification of these putative DC precursors will allow analysis of the early phases of DC hemopoiesis, whereas the characterization of the MLR-stimulatory cells in human BM will be of major importance in the understanding of BM transplant failure and graft-vs-host disease.
 ...
PMID:Identification of potent mixed leukocyte reaction-stimulatory cells in human bone marrow. Putative differentiation stage of human blood dendritic cells. 845 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>