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131.
Self peptides bound to self major histocompatibility complex (MHC) molecules have been implicated both in positive and in negative selection of T cells during intrathymic development. We report here that the novel MHC-restricted monoclonal antibody Y-Ae detects the MHC class II bound form of a major self peptide. Y-Ae binds approximately 12% of the relevant MHC class II molecules on self antigen presenting cells. The peptide detected by Y-Ae is one of several major peptides eluted from the MHC molecule. These data suggest that self peptides presented by self MHC class II molecules at densities sufficient to signal a CD4 T cell are of very limited complexity. Furthermore, as Y-Ae stains antigen presenting cells that mediate negative selection but not thymic cortical epithelial cells that drive positive selection, differential expression of self peptide:self MHC class II complexes may be a key feature of intrathymic selection. 相似文献
132.
Homeobox gene expression correlated with the bifurcation process of limb cartilage development. 总被引:9,自引:0,他引:9
The complex architecture of the limb cartilage pattern probably develops by the sequential segmentation and branching process of precartilaginous cell condensation under the control of positional signalling provided by the zone of polarizing activity (anteroposterior) and the apical ectodermal ridge (proximodistal). This signalling is monitored and interpreted in the mesenchymal cells and induces the position-specific response of subsets of genes. Homeobox genes may be responsible for the interpretation of signalling. A correlation between limb pattern and expression domains of the homeobox genes in the upstream region of Hox/Chox-4 has been proposed. We have analysed the spatial expression pattern of the Chox-1 genes during development of chick limb buds. In contrast to genes in Hox/Chox-4 expressed coordinately along the anteroposterior axis, homeobox genes in Chox-1 have unique and mutually exclusive expression domains along the proximodistal axis. We report here that the expression domains of the Chox-1 genes are closely related to the segmental structure of cartilage along the proximodistal axis, whereas the expression domains of the Chox-4 genes are related to the cartilage branching pattern. 相似文献
133.
Most eukaryotic cells produce proteins with relative molecular masses in the range of 100,000 to 110,000 after exposure to high temperatures. These proteins have been studied only in yeast and mammalian cells. In Saccharomyces cerevisiae, heat-shock protein hsp104 is vital for tolerance to heat, ethanol and other stresses. The mammalian hsp110 protein is nucleolar and redistributes with growth state, nutritional conditions and heat shock. The relationships between hsp110, hsp104 and the high molecular mass heat-shock proteins of other organisms were unknown. We report here that hsp104 is a member of the highly conserved ClpA/ClpB protein family first identified in Escherichia coli and that additional heat-inducible members of this family are present in Schizosaccharomyces pombe and in mammals. Mutagenesis of two putative nucleotide-binding sites in hsp104 indicates that both are essential for function in thermotolerance. 相似文献
134.
Enhancement of T-cell activation by the CD43 molecule whose expression is defective in Wiskott-Aldrich syndrome 总被引:9,自引:0,他引:9
J K Park Y J Rosenstein E Remold-O'Donnell B E Bierer F S Rosen S J Burakoff 《Nature》1991,350(6320):706-709
CD43 (sialophorin, leukosialin, leukocyte large sialoglycoprotein), a heavily sialylated molecule found on most leukocytes and platelets, was initially identified as a major glycoprotein of mouse, rat and human T cells. CD43 expression is defective on the T cells of males with the Wiskott-Aldrich syndrome, an X chromosome-linked recessive immunodeficiency disorder. Affected males are susceptible to opportunistic infections and do not respond to polysaccharide antigens, reflecting defects in cytotoxic and helper T-cell functions. Anti-CD43 monoclonal antibodies have a modest costimulatory effect on T cells, natural killer cells, B cells and monocytes, and one such antibody has been shown to activate T cells directly. To investigate a possible physiological role for CD43, a complementary DNA encoding the human protein was introduced into an antigen-responsive murine T-cell hybridoma. We observed that CD43 enhances the antigen-specific activation of T cells and that the intracellular domain of CD43, which is hyperphosphorylated during T-cell activation, is required for this function. We also found that antigen-presenting cells can bind specifically to immobilized purified CD43 and that the binding can be inhibited by liposomes containing CD43 as well as by anti-CD43 monoclonal antibodies. 相似文献
135.
The bcl-2 gene encodes a novel G protein 总被引:5,自引:0,他引:5
Little is known about the biochemical or functional nature of the proteins encoded by the bcl-2 gene, which undergoes chromosomal translocation in approximately 85% of follicular lymphoma, 20% of diffuse large cell lymphoma and 10% of chronic lymphocytic leukaemia of B cells. Translocation of bcl-2 sequences from chromosome 18 to the JH segment of the immunoglobulin gene at chromosome band 14q32 in B cells results in deregulated expression of this gene, causing high steady state levels of bcl-2 messenger RNA2. DNA sequence data indicate that bcl-2 encodes two proteins by virtue of alternative splicing, designated as Bcl-2 alpha and Bcl-2 beta, with relative molecular masses of 26,000 and 22,000 respectively. Cell fractionation experiments indicate that the bcl-2 alpha gene product is located at the inner surface of the cell membrane, suggesting a possible role in mitogenic signal transduction. We report here that Bcl-2 alpha has GTP-binding activity and a protein sequence that suggests it belongs to the small molecular weight GTP-binding protein (G protein) family. 相似文献
136.
Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria 总被引:107,自引:0,他引:107
M Y Cheng F U Hartl J Martin R A Pollock F Kalousek W Neupert E M Hallberg R L Hallberg A L Horwich 《Nature》1989,337(6208):620-625
A nuclear encoded mitochondrial heat-shock protein hsp60 is required for the assembly into oligomeric complexes of proteins imported into the mitochondrial matrix. hsp60 is a member of the 'chaperonin' class of protein factors, which include the Escherichia coli groEL protein and the Rubisco subunit-binding protein of chloroplasts. 相似文献
137.
In vitro ecdysteroid production by dissociated Y-organ cells of the shore crabCarcinus maenas was characterized during short-term incubations. Under optimized conditions (M199 adjusted to crab osmolality and with the addition of 10% foetal calf serum), ecdysteroid production by dispersed cells increased linearly during 4-hour incubations, with little intra-assay variation. 25-deoxyecdysone was mainly produced. PurifiedCarcinus molt inhbiting hormone (CamMIH) produced a dose-dependent inhibition of ecdysteroid production by dispersed cells. The cells were about 50 times more sensitive than whole glands to MIH. Other structurally-related peptides were tested. 相似文献
138.
H. Miyamoto N. Manabe Y. Akiyama T. Watanabe M. Sugimoto E. Sato 《Cellular and molecular life sciences : CMLS》1994,50(9):808-811
The morphometric parameters of spermatogenic cells in a mouse strain prone to accelerated senescence (SAM-P), a novel murine model of spontaneously promoted aging, were compared with those of a SAM resistant strain (SAM-R) after birth until 40 weeks (mean life span of SAM-P). A mixture of gonocytes and spermatogonia were present in the testis in 1-week-old mice, and no gonocytes were observed in 2-week-old mice. At 6 weeks of age, the absolute number of spermatogonia in SAM-P was 27% greater than that in SAM-R, whereas the cell number in 40-week-old SAM-P was 17% less than in SAM-R. Primary spermatocytes were first observed in 3-week-old animals, and the cell numbers in SAM-P at 3, 5 and 6 weeks were 78%, 31% and 25%, respectively, greater than in SAM-R, whereas the cell number in SAM-P at 40 weeks was 30% less than SAM-R. Round spermatids were first observed in all SAM-P at 4 weeks old, but 20% of SAM-r had no spermatids and the rest had only a few. At 5 and 6 weeks old, the absolute numbers of round spermatids in SAM-P was about 34% and 41%, respectively, greater than in SAM-R, whereas the cell number in 40-week-old SAM-P was about 34% less than SAM-R. These results indicate that testicular maturation begins at an earlier age in SAM-P than SAM-R. Furthermore, at the age of 40 weeks signs of testicular deterioration are evident in SAM-P mice only 相似文献
139.
A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies 总被引:90,自引:0,他引:90
Mitochondrial encephalomyopathies are usually divided into three distinct clinical subgroups: (1) mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS); (2) myoclonus epilepsy associated with ragged-red fibres (MERRF); and (3) chronic progressive external ophthalmoplegia (CPEO) including Kearns-Sayre syndrome. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNA(Leu)(UUR) that is specific to patients with MELAS. Because this mutation creates an ApaI restriction site, we could perform a simple molecular diagnostic test for the disease. The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested. Southern blot analysis confirmed that the mutant DNA always coexists with the wild-type DNA (heteroplasmy). 相似文献
140.
In the host cell, retroviral DNAs exist in three main forms: unintegrated linear, unintegrated circular, and integrated (the provirus). High levels of unintegrated forms of retroviral DNA often correlate with superinfection and accompanying cytopathic effects, as, for example, in the case of feline acquired immunodeficiency. In culture, HIV-1 infection also results in high levels of unintegrated viral DNA although direct correlations with cytopathicity have not been made. The low frequency of HIV-1-infected cells in patients has made it difficult to determine the structure of the viral DNA in fresh tissue samples from AIDS patients by standard methods such as Southern hybridization. The PCR technique however, which allows the detection of viral DNA at levels far below that possible by other hybridization methods is, in its conventional form, of limited use for quantitative analysis. To study the amount and form of HIV-1 DNA in primary tissue of AIDS patients we have therefore modified the PCR method. Our results indicate that each of the three species of viral DNA are detectable in blood and brain of AIDS patients, and that in autopsy samples from patients with HIV encephalitis there is a considerably higher proportion of unintegrated viral DNA. 相似文献