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)

We here demonstrate that ligand binding to MHC class I molecules induces homotypic cell adhesion of lymphocytes and monocytes. mAb to beta 2-microglobulin caused sustained, largely LFA-1-independent adhesion whereas mAb to the MHC class I alpha H chain caused transient LFA-1-dependent adhesion. Both the protein kinase C inhibitor sphingosine and the tyrosine kinase inhibitor genistein abrogated MHC class I-mediated cellular adhesion. These results indicate that MHC class I molecules transduce signals that induce cell adhesion and suggest that interaction between MHC class I-restricted T cells and APC may result in reciprocal enhanced adhesiveness of these cells.
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PMID:Engagement of MHC class I molecules induces cell adhesion via both LFA-1-dependent and LFA-1-independent pathways. 154 17

Cis-dichlorodiammine platinum (CDDP) has recently been introduced for the treatment of human malignancies. CDDP belongs to the group of heavy metals and has nephrotoxicity, whose side effects limit the dose that can be used in patients. The urinary excretion of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), arylamidase (AA) activity and beta 2-microglobulin was determined in ovarian cancer patients receiving sequential combination chemotherapy with CDDP, adriamycin (ADM) and cyclophosphamide (CPA) (PAC chemotherapy) to evaluate the sensitivity of these indices for acute renal tubular damage and compared with the change in serum BUN, Cr and Ccr values. Increases in enzyme excretion after PAC chemotherapy were more often noticed and the urinary enzyme activity varied up to the 10.4-fold of the control, while serum BUN, Cr and Ccr values remained almost within normal limits. Enzyme excretion returned almost to the normal value in one week. A comparison between the urinary enzyme excretion especially AA value and serum BUN, Cr and Ccr values indicated that the serial determination of the urinary AA excretion pattern is more useful in detecting CDDP-induced nephrotoxicity than that of serum BUN, Cr and Ccr values.
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PMID:[Cisplatin and ovarian carcinoma--early detection of cisplatin-induced nephrotoxicity]. 404 May 42

Dendritic cells (DC) are potent APCs, able to induce efficiently primary T cell-mediated responses to foreign Ags. To assess the efficiency of DC, as compared with other APC types, in the in vivo presentation of self-Ags to CD4+ T cells, we analyzed processing and presentation to class II-restricted T cells of endogenous naturally processed self-epitopes constitutively expressed by mouse APC. Mouse beta 2-microglobulin (m beta 2-m) peptides corresponding to residues 26-39 and 24-36 are constitutively presented, in mice expressing m beta 2-m, by I-Ad and I-Ed molecules respectively, as demonstrated by activation of m beta 2-m-specific T cell hybridomas generated in BALB/c beta 2-m-deficient mice. These dominant, naturally processed self-epitopes of m beta 2-m are presented by APC from a variety of tissues, including the thymus. To analyze the relative efficiency of different APC populations in the presentation of self-beta 2-m, the ability of purified DC, macrophages, and large or small B cells to stimulate m beta 2-m-specific T cell hybridomas was tested. Naturally processed self-m beta 2-m epitopes are constitutively presented to T cells by any class II-positive APC tested, but with highest efficiency by splenic and thymic DC, followed by macrophages, large B cells, and small B cells. This hierarchy of self-beta 2-m presentation does not depend on differential processing capacity of these APC populations, and it correlates with expression of CTLA-4 ligands and ICAM-1 molecules, rather than with expression of class II molecules.
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PMID:Dendritic cells are the most efficient in presenting endogenous naturally processed self-epitopes to class II-restricted T cells. 752 78

The mouse beta 2-microglobulin (m beta 2-m) peptide corresponding to residues 25-40 binds to the MHC class II molecules I-Ad and I-Ed and is immunogenic in BALB/c beta 2-m-deficient but not in normal BALB/c mice. The self-m beta 2-m peptide 25-40 is presented by both I-Ad and I-Ed class II molecules as demonstrated by the activation of T cell hybridomas specific for this sequence obtained from beta 2-m knock-out mice. By analyzing the effect of N- and C-terminal truncations of m beta 2-m25-40 on binding to class II molecules and on activation of T cell hybridomas, the minimum epitopes recognized by I-Ad and I-Ed-restricted T cells are included within amino acid residues 26-39 and 24-36, respectively. Both sets of T hybridomas are also activated by the corresponding naturally processed self-epitope presented by APC from BALB/c mice and from other H-2d strains, irrespective of their Mls phenotype. Therefore, the sequence 25-40 contains dominant naturally processed self-epitopes of the mouse beta 2-m. Processing of endogenous m beta 2-m is sensitive to protease inhibitors and lysosomotropic amines, and is not caused by reuptake of shed or released protein. These results indicate that self-beta 2-m-peptide-MHC class II complexes derive from constitutive processing of the endogenous intracellular pool of m beta 2-m in an acidic endosomal compartment. Antigenic complexes between m beta 2-m peptides and I-Ad or I-Ed class II molecules are constitutively expressed by APC of different tissues, including the thymus, and they are able to induce T cell tolerance, as shown by the lack of T cell response to m beta 2-m25-40 in BALB/c mice.
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PMID:Constitutive presentation of dominant epitopes from endogenous naturally processed self-beta 2-microglobulin to class II-restricted T cells leads to self-tolerance. 781 67