Abstract:
:The antigen recognition of a profoundly immunosuppressive mAb, mAb 2E1, in vivo was investigated. In addition to the 62-kDa effector cell protease receptor 1, mAb 2E1 bound the 32-kDa T cell adhesion receptor E2 (CD99) and the 86-kDa p80 subunit of the nuclear antigen complex Ku. These molecules share no overall sequence similarity. Peptide mapping experiments identified the mAb 2E1 cross-reacting epitopes as the sequences 66GSFSDADLAD75 in E2 and 571GGAHFSVSSLAEG583 in p80 of Ku, sharing a minimal homology motif FSXXXLA, in which X is a nonconserved amino acid. Each of these peptides separately inhibited the binding of mAb 2E1 to E2, effector cell protease receptor 1, and p80 of Ku in a dose-dependent manner. Scatchard plot analysis of 125I-labeled mAb 2E1 binding to peripheral blood mononuclear cells revealed a high-affinity interaction with a dissociation constant of 7 x 10(-10) M. An anti-E2 mAb bound the same epitope 66GSFSDADLAD75 recognized by mAb 2E1 but failed to react with p80 of Ku and was not immunosuppressive. These findings demonstrate that high-affinity cross-reacting mAbs can be generated by mimicry of a minimal surface on unrelated molecules. This model of minimal mimicry may determine the nuclear reactivity of certain autoantibodies to Ku and contribute to aberrant immunosuppression in vivo.
journal_name
Proc Natl Acad Sci U S Aauthors
Rothermel AL,Altieri DCdoi
10.1073/pnas.95.7.3816subject
Has Abstractpub_date
1998-03-31 00:00:00pages
3816-20issue
7eissn
0027-8424issn
1091-6490journal_volume
95pub_type
杂志文章abstract::Herpes simplex virus type 2 (HSV-2) DNA was treated with four restriction endonucleases (EcoRI, HincIII, Bgl II, and Xba I) and eight fragments were purified and labeled with 32P in vitro. The kinetics of renaturation of each of the fragments was measured in the presence of DNA extracted from 333-8-9, a hamster cell l...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.2.880
更新日期:1980-02-01 00:00:00
abstract::Antibodies have been prepared to the core protein of cartilage chondroitin sulfate proteoglycan from clones isolated after fusion of rat spleen cells and mouse myeloma cell lines. Antibodies produced by five clones were studied in detail by a radioimmunoassay utilizing 35SO42-labeled hyaluronidase-digested chondroitin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.7.3971
更新日期:1980-07-01 00:00:00
abstract::Sequence polymorphism of class II major histocompatibility complex-encoded molecules (Ia) not only accounts for the allelic variability in Ia structure relevant to T-lymphocyte responses but also seems to result in differential quantitative expression of particular Ia heterodimers. The contributions of different allel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.9.2921
更新日期:1987-05-01 00:00:00
abstract::A nongenetic, transgenerational effect of parental age on offspring fitness has been described in many taxa in the laboratory. Such a transgenerational fitness effect will have important influences on population dynamics, population age structure, and the evolution of aging and lifespan. However, effects of parental a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1422715112
更新日期:2015-03-31 00:00:00
abstract::Endocytic protein trafficking is directed by sorting signals on cargo molecules that are recognized by cytosolic adaptor proteins. However, the steps necessary to segregate the variety of cargoes during endocytosis remain poorly defined. Using Caenorhabditis elegans, we demonstrate that multiple plasma membrane endocy...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1302918110
更新日期:2013-07-16 00:00:00
abstract::The use of molecular methods is altering our understanding of the microbial biosphere and the complexity of the tree of life. Here, we report a newly discovered uncultured plastid-bearing eukaryotic lineage named the rappemonads. Phylogenies using near-complete plastid ribosomal DNA (rDNA) operons demonstrate that thi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1013337108
更新日期:2011-01-25 00:00:00
abstract::Glycoprotein E (gE) of HSV plays a key role in cell-to-cell spread and virus-induced cell fusion. Here, we report that this function of gE requires the cooperation of tegument proteins UL11, UL16, and UL21. We found that the four proteins come together with very high efficiency to form a complex in transfected cells a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1212900109
更新日期:2012-11-27 00:00:00
abstract::Through a process called "bioturbation," burrowing macrofauna have altered the seafloor habitat and modified global carbon cycling since the Cambrian. However, the impact of macrofauna on the community structure of microorganisms is poorly understood. Here, we show that microbial communities across bioturbated, but ge...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1917494117
更新日期:2020-07-07 00:00:00
abstract::The substrate specificity of the catalytic subunit of rabbit skeletal muscle 3': 5'-cyclic AMP-dependent protein kinase (EC 2.7.1.37; ATP: protein phosphotransferase) has been studied using the synthetic peptide Arg-Gly-Tyr-Ser-Leu-Gly corresponding to the sequence around serine 24, a phosphorylation site in reduced, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.4.1038
更新日期:1976-04-01 00:00:00
abstract::Hepatitis B virus (HBV) is a major human pathogen. In addition to its importance in human health, there is growing interest in adapting HBV and other viruses for drug delivery and other nanotechnological applications. In both contexts, precise biophysical characterization of these large macromolecular particles is fun...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0800406105
更新日期:2008-07-08 00:00:00
abstract::Individual proteins can now often be modified with atomic precision, but there are still major obstacles to connecting proteins into larger assemblies. To direct protein assembly, ideally, peptide tags would be used, providing the minimal perturbation to protein function. However, binding to peptides is generally weak...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1315776111
更新日期:2014-04-01 00:00:00
abstract::Standard economic and evolutionary models assume that humans are fundamentally selfish. On this view, any acts of prosociality--such as cooperation, giving, and other forms of altruism--result from covert attempts to avoid social injunctions against selfishness. However, even in the absence of social pressure, individ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.1112324108
更新日期:2011-12-06 00:00:00
abstract::Using chimeric recombinants transfected into HeLa cells and a transient expression assay, we demonstrate that the 5'-flanking region of the pS2 gene from position -428 to position -324 exhibits both constitutive and estrogen-inducible enhancer activity. The estrogen-inducible activity, but not the constitutive activit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.4.1218
更新日期:1989-02-01 00:00:00
abstract::Neuropilin-1 (NRP1) is a 130-kDa transmembrane receptor for semaphorins, mediators of neuronal guidance, and for vascular endothelial growth factor 165 (VEGF(165)), an angiogenesis factor. A 2.2-kb truncated NRP1 cDNA was cloned that encodes a 644-aa soluble NRP1 (sNRP1) isoform containing just the a/CUB and b/coagula...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.040337597
更新日期:2000-03-14 00:00:00
abstract::Contact of axons with target territories results in the formation of synapses, specific junctional complexes that may represent a final stage of neuronal maturation. Synaptosomal-associated protein 25 (SNAP-25) is a component of particular nerve terminals recently identified in rodent brain. To evaluate the structure ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.3.785
更新日期:1991-02-01 00:00:00
abstract::A comparison of five constant region sequences of human and mouse k and lambda immunoglobulin chains has been undertaken in order to reveal sequence homologies and evolutionary relationships. Simultaneously, a comparison with the three-dimensional structure of one mouse k-chain (McPC 603) has suggested structural reas...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.7.2785
更新日期:1975-07-01 00:00:00
abstract::To initiate fertilization, mouse sperm bind to Ser- (O-) linked oligosaccharides located at the sperm combining site of zona pellucida glycoprotein mZP3. Apparently, the oligosaccharides are present on one or more of five Ser residues clustered in the carboxyl-terminal region of the mZP3 polypeptide. Here, each of the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.11.6193
更新日期:1998-05-26 00:00:00
abstract::We have studied the involvement of the 5' cap structure in the splicing of precursor mRNAs in a HeLa nuclear extract. We show that precursor mRNAs are spliced efficiently only when they possess a cap structure and that preincubation of a HeLa nuclear extract rendered the splicing reaction highly sensitive to inhibitio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.22.7590
更新日期:1985-11-01 00:00:00
abstract::A purified rabbit liver membrane protein that binds desialylated glycoproteins has been shown to be a mitogen for human peripheral lymphocytes. The mitogenic activity is specific for desialylated thymus-derived (T)-cells. The loss of mitogenicity upon exposure of the binding protein to neuraminidase and the inhibitory...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.2.676
更新日期:1977-02-01 00:00:00
abstract::The involvement of p53 in regulating diverse cellular processes dictates that it must respond to multiple signaling mechanisms, thus coordinating the response to various "stress conditions." Genotoxic stress has served as a paradigm to dissect the transactivation-dependent branch of the pathway by which p53 can induce...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.9.4675
更新日期:1997-04-29 00:00:00
abstract::Phosphorylation of ADP to ATP was induced in nonrespiring submitochondrial particles (SMP) from rat liver by the application of electric pulses with field strengths of 10-35 kV/cm and a decay time of 60 mus. In all cases respiration was inhibited completely by using cyanide or rotenone. Newly formed ATP was measured b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.12.7473
更新日期:1981-12-01 00:00:00
abstract::Gamma-Glutamyl transpeptidase, which consists of two nonidentical subunits, is rapidly inactivated with respect to its transpeptidase and hydrolase activities by the gamma-glutamyl analogs 6-diazo-5-oxo-L-norleucine and L-azaserine. Inactivation, which is prevented by gamma-glutamyl substrates (but not by acceptor sub...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.3.931
更新日期:1977-03-01 00:00:00
abstract::Studies of the accelerated aging disorder Hutchinson-Gilford progeria syndrome (HGPS) can potentially reveal cellular defects associated with physiological aging. HGPS results from expression and abnormal nuclear envelope association of a farnesylated, truncated variant of prelamin A called "progerin." We surveyed the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1809683116
更新日期:2019-02-26 00:00:00
abstract::Neovascular diseases of the retina include age-related macular degeneration and diabetic retinopathy, and together they comprise the leading causes of adult-onset blindness in developed countries. Current surgical, pharmaceutical, and laser therapies for age-related macular degeneration (AMD) rarely result in improved...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.122247299
更新日期:2002-06-25 00:00:00
abstract::Mannan-binding protein (MBP), a Ca2+-dependent mammalian lectin specific for mannose and N-acetylglucosamine, is an important serum component associated with innate immunity. MBP activates complement and functions as a direct opsonin on binding to mannooligosaccharide-bearing pathogens. We have found that MBP recogniz...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.2.371
更新日期:1999-01-19 00:00:00
abstract::Management of the diverse fisheries of the world has had mixed success. While managing single species in data-rich environments has been largely effective, perhaps the greatest challenge facing fishery managers is how to deal with mixed stocks of fish with a range of life histories that reside in the same location. Be...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1705169114
更新日期:2017-08-22 00:00:00
abstract::Although the role of APP and PSEN genes in genetic Alzheimer's disease (AD) cases is well established, fairly little is known about the molecular mechanisms affecting Abeta generation in sporadic AD. Deficiency in Abeta clearance is certainly a possibility, but increased expression of proteins like APP or BACE1/beta-s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0710263105
更新日期:2008-04-29 00:00:00
abstract::Gene regulatory networks (GRNs) provide a transformation function between the static genomic sequence and the primary spatial specification processes operating development. The regulatory information encompassed in developmental GRNs thus goes far beyond the control of individual genes. We here address regulatory info...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1610616114
更新日期:2017-06-06 00:00:00
abstract::Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can naturally or therapeutica...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0500098102
更新日期:2005-02-22 00:00:00
abstract::Land-use change is a major driver of biodiversity loss worldwide. Although biodiversity often shows a delayed response to land-use change, previous studies have typically focused on a narrow range of current landscape factors and have largely ignored the role of land-use history in shaping plant and animal communities...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1910023117
更新日期:2020-01-21 00:00:00