Abstract：
:Structures of two intact monoclonal antibodies were solved by X-ray diffraction analysis revealing, in both cases, the dispositions of all segments, as well as the structures of the hinge polypeptides. An IgG1, whose antigen is the drug phenobarbital, assumed a completely different conformation when compared with an IgG2a specific for canine lymphoma cells. Though neither IgG displays global two-fold symmetry, both maintain two pseudo dyad axes, one relating Fab segments, and the other the halves of the Fc. In both IgGs, the Fc segment is obliquely disposed with respect to the plane of the Fabs, making an angle of 128 degrees in the IgG2a, and 107 degrees in the IgG1. Hinge angles of the IgG1 are notably different at 78 degrees and 123 degrees, and unique as well from IgG2a values of 66 degrees and 113 degrees. Elbow angles within the IgG1 Fabs are the same at 155 degrees, but non-identical in IgG2a where they took on values of 143 degrees and 159 degrees. The IgG2a has an angle of 172 degrees between Fabs so that it exhibits a "distorted T" shape, whereas that angle in the IgG1 is a much more acute 115 degrees producing a "distorted Y". CH2 domains appear, in both antibodies, to be the most independently mobile of the paired IgG domains. This perhaps reflects their importance in modulating effector functions through exposure of binding loci on the CH2, at the CH2-CH3 interface, and on lower hinge polypeptides. Hinges in both antibodies contain disulfide-linked cores bounded by fluid regions above and below, which provide mobility to the Fabs and Fc respectively. The conformations seen in these two structures are undoubtedly only two among many but they illustrate the modes of flexibility inherent to the IgG architecture.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Harris LJ,Larson SB,Skaletsky E,McPherson Adoi
10.1111/j.1600-065x.1998.tb01186.xsubject
Has Abstractpub_date
1998-06-01 00:00:00pages
35-43eissn
0105-2896issn
1600-065Xjournal_volume
163pub_type
杂志文章,评审abstract：:Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by immune-mediated destruction of the biliary epithelial cells (BEC) lining the intrahepatic bile ducts (non-suppurative destructive cholangitis (NSDC)). Autoantibody and autoreactive T-cell responses specific for the self-antigen pyruvate de...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-0528.2002.00021h.x
更新日期：2000-04-01 00:00:00
abstract：:A byproduct of the largely stochastic generation of a diverse B-cell specificity repertoire is production of cells that recognize autoantigens. Indeed, recent studies indicate that more than half of the primary repertoire consists of autoreactive B cells that must be silenced to prevent autoimmunity. While this silenc...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2010.00936.x
更新日期：2010-09-01 00:00:00
abstract：:The infiltration of human tumors by T cells is a common phenomenon, and over the past decades, it has become increasingly clear that the nature of such intratumoral T-cell populations can predict disease course. Furthermore, intratumoral T cells have been utilized therapeutically in clinical studies of adoptive T-cell...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12140
更新日期：2014-01-01 00:00:00
abstract：:Upon antigen recognition, T cells undergo substantial membrane and cytoskeletal rearrangements that lead to the formation of the immunological synapse and are necessary for subsequent T-cell activation. However, little is known about how membrane and cytoskeletal molecules interact during these processes. Here we disc...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.18911.x
更新日期：2002-11-01 00:00:00
abstract：:Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside-out signal transduction pathways leading to integrin-dependent adhesion. Integrin activation by chemokines is very rapid, is downmodulated within minutes and appears to involve both enhanced heterodimer latera...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.18604.x
更新日期：2002-08-01 00:00:00
abstract：:Interleukin-12 (IL-12) and IL-23 share a common chain. Yet, their production in response to pathogens is differentially regulated, and their functions are distinct and often antithetic. IL-12 is involved in the induction or amplification of the T-helper (Th) type 1 response, whereas IL-23 has been associated with the ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00700.x
更新日期：2008-12-01 00:00:00
abstract：:Apoptosis is an important component of normal tissue physiology, and the prompt removal of apoptotic cells is equally essential to avoid the undesirable consequences of their accumulation and disintegration. Professional phagocytes are highly specialized for engulfing apoptotic cells. The recent ability to track cells...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12537
更新日期：2017-05-01 00:00:00
abstract：:Clarifying the signals that lead to dendritic cell (DC) development and identifying cellular intermediates on their way to DC differentiation are essential steps to understand the dynamic regulation of number, localization, and functionality of these cells. In the past decade, much knowledge on cytokines, transcriptio...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2009.00877.x
更新日期：2010-03-01 00:00:00
abstract：:Five of the 10 human Toll-like receptors (TLRs) (TLR3, TLR4, TLR7, TLR8, and TLR9), and four of the 12 mouse TLRs (TLR3, TLR4, TLR7, TLR9) can trigger interferon (IFN)-alpha, IFN-beta, and IFN-lambda, which are critical for antiviral immunity. Moreover, TLR3, TLR7, TLR8, and TLR9 differ from TLR4 in two particularly i...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2007.00564.x
更新日期：2007-12-01 00:00:00
abstract：:Innate lymphoid cells (ILC) are a recently identified group of innate lymphocytes that are preferentially located at barrier surfaces. Barrier surfaces are in direct contact with complex microbial ecosystems, collectively referred to as the microbiota. It is now believed that the interplay of the microbiota with host ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12580
更新日期：2017-09-01 00:00:00
abstract：:Unique Vγ2Vδ2 (Vγ9Vδ2) T cells existing only in human and non-human primates, account for the majority of circulating γδ T cells in human adults. Vγ2Vδ2 T cells are the sole γδ T-cell subpopulation capable of recognizing the microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by selected pathoge...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12927
更新日期：2020-11-01 00:00:00
abstract：:GITR [glucocorticoid inducible tumor necrosis factor receptor (TNFR)-related protein] and 4-1BB are costimulatory TNFR family members that are expressed on regulatory and effector T cells as well as on other cells of the immune system. Here we discuss the role of GITR and 4-1BB on T cells during viral infections and i...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01063.x
更新日期：2011-11-01 00:00:00
abstract：:Innate lymphoid cells (ILCs) constitute a family of effectors in innate immunity and regulators of tissue remodeling that have a cytokine and transcription factor expression pattern that parallels that of the T-helper (Th) cell family. Here, we discuss how ILCs can be categorized and summarize the current knowledge of...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12034
更新日期：2013-03-01 00:00:00
abstract：:Thymic dendritic cells (DC) mediate negative selection at a relatively late stage of the T-cell developmental pathway. We present evidence that the development of thymic DC and of T-lineage cells is linked via a common precursor at an early stage of thymocyte development. T-lineage precursor populations from the adult...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01228.x
更新日期：1998-10-01 00:00:00
abstract：:The cellular and molecular mechanisms underlying the formation of distinct central, effector, and exhausted CD8+ T-cell memory subsets were first described in the setting of acute and chronic viral diseases. The role of these T-cell memory subsets are now being illuminated as relevant to the tumor-bearing state. The g...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2006.00391.x
更新日期：2006-06-01 00:00:00
abstract：:Studies of the regulation of gene expression historically focused on transcription. However, during stress and apoptosis, profound gene expression changes occur more rapidly and globally than is possible by regulating transcription. Posttranscriptional changes in mRNA processing and translation in response to diverse ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12052
更新日期：2013-05-01 00:00:00
abstract：:There is now convincing evidence that autoreactive CD8+ T cells can contribute to the pathogenesis of organ-specific autoimmune diseases. In the non-obese diabetic mouse, there is direct evidence that beta-islet cell-specific CD8+ cytotoxic T cells have a pathogenic effect. In human diseases such as autoimmune diabete...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01308.x
更新日期：1999-06-01 00:00:00
abstract：:B-cell depletion therapy has beneficial effects in autoimmune diseases. This is only partly explained by an elimination of autoantibodies. How does B-cell depletion improve disease? Here, we review preclinical studies showing that B cells can propagate autoimmune disorders through cytokine production. We also highligh...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12374
更新日期：2016-01-01 00:00:00
abstract：:T cells are key players of the mammalian adaptive immune system. They experience different mechanical microenvironments during their life cycle, from the thymus, secondary lymph organs, and peripheral tissues that are free of externally applied force, but display variable substrate rigidities to the blood and lymphati...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12122
更新日期：2013-11-01 00:00:00
abstract：:The cellular communications between a human CD4+ clone and autologous CD4+ clones induced with the first clone are described. The autoreactive clones proliferated after stimulation with the inducer clone, but not after stimulation with autologous clones expressing irrelevant specificities. The inducer clone markedly l...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1990.tb00804.x
更新日期：1990-08-01 00:00:00
abstract：:BioBreeding (BB) rats spontaneously develop an autoimmune diabetic syndrome similar to that observed in humans and NOD mice. One of the diabetes susceptibility loci maps to the lyp locus on chromosome 4. In this article we describe the consequences of the BB rat lyp mutation on T-cell homeostasis, repertoire and funct...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.1840115.x
更新日期：2001-12-01 00:00:00
abstract：:Since the discovery that the recombination-activating gene (RAG) proteins were capable of transposition in vitro, investigators have been trying to uncover instances of transposition in vivo and understand how this transposase has been harnessed to do useful work while being inhibited from causing deleterious chromoso...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2004.00161.x
更新日期：2004-08-01 00:00:00
abstract：:αβ T cells are an integral part of protective immunity against pathogens. After precursor cells arise in the adult bone marrow or fetal liver, they migrate to the thymus where they rearrange their T-cell receptor genes (TCR) and undergo selection on the basis of their interactions with ligands expressed by thymic stro...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12095
更新日期：2013-09-01 00:00:00
abstract：:IgG dimers occurring in therapeutic Ig preparations have been characterized as Id-anti-Id, in that the sites of interaction are localized to the distal tips of the Fab arms. The observation that such dimers are prevalent in Ig or Igi.v. prepared from large plasma pools, but absent in preparations from a single individ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1994.tb00861.x
更新日期：1994-06-01 00:00:00
abstract：:NF-κB proteins were identified in the search for mechanisms that regulate B-lymphocyte-specific transcription of immunoglobulin κ light chain genes. Twenty-five years later, though the function of the κB site in the enhancer remains enigmatic, NF-κB proteins have been shown to have important roles in B-cell developmen...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2012.01106.x
更新日期：2012-03-01 00:00:00
abstract：:Cells of the monocyte/macrophage system originate from the bone marrow, reach the organs via the blood, immigrate through postcapillary venules and further differentiate into organ-specific tissue macrophages. In rats and other species, activated monocytes/macrophages aggravate autoimmune reactions, rejection of non-v...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.1840104.x
更新日期：2001-12-01 00:00:00
abstract：:In the human, most IgM+IgD+ as well as CD5+ peripheral blood B cells express unmutated V genes and thus can be assigned to a pre-germinal centre (GC) stage of development. The memory B-cell compartment generated in the GC reaction and characterized by cells bearing somatically mutated V-region genes consists not only ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01447.x
更新日期：1998-04-01 00:00:00
abstract：:The H-2 restricted nature of the cytotoxic T cell responses to the HY antigen in mice has been reviewed, together with mapping data for the H-2 K and/or D association of responses to male cells of the following haplotypes: H-2b, H-2d, H-2k, H-2s. Ir gene complementation is implicated in the HY response of a number of ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1977.tb00235.x
更新日期：1977-01-01 00:00:00
abstract：:The major histocompatibility complex (MHC) plays a central role in controlling immune responsiveness, susceptibility to certain diseases and histo-incompatibility. A physical map of the complete rat MHC, the RTI complex, is presented based on a PAC clonal contig (RT1n haplotype). Expression profiling of various tissue...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.1840108.x
更新日期：2001-12-01 00:00:00
abstract：:CD69 has been known as an early activation marker of lymphocytes; whereas, recent studies demonstrate that CD69 also has critical functions in immune responses. Early studies using human samples revealed the involvement of CD69 in various inflammatory diseases including asthma. Moreover, murine disease models using Cd...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12559
更新日期：2017-07-01 00:00:00
