Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different from that of antimicrobial TCRs. Rather than being centered on the peptide-major histocompatibility complex, this TCR contacted only the N-terminal peptide segment and made asymmetrical interactions with the major histocompatibility complex helices. The interaction was dominated by the hypervariable complementarity-determining region 3 loops, indicating that unconventional topologies are possible because of the unique complementarity-determining region 3 sequences created during rearrangement. This topology reduces the interaction surface with peptide and alters the geometry for CD4 association. We propose that unusual TCR-binding properties can permit autoreactive T cells to escape deletion.
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PMID:Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. 1584 98

The biological purpose of the mature, postthymic CD8(+) T cell is to respond to microbial antigens with a developmental program of clonal expansion and concomitant differentiation leading to effector cells (T(EFF)) that provide antimicrobial defense. Because many microbial infections persist into a chronic phase, this antigen-stimulated developmental program must be capable of continually generating T(EFF), perhaps for the lifetime of the individual. This chapter proposes that the ability of a CD8(+) T cell clone to maintain the continual production of T(EFF) during periods of persistent antigenic stimulation is based on a program that has two sequential phases of clonal expansion: an initial stage that occurs mainly in the secondary lymphoid tissues and is mediated by ligation of the T cell receptor (TCR) and CD27, and a subsequent, IL-2-dependent phase that occurs predominantly in peripheral, nonlymphoid tissues. The TCR/CD27-dependent phase establishes a nondifferentiating, self-renewing pool of clonally expanding cells, and the IL-2-dependent phase mediates continued clonal expansion that is coupled to the development of T(EFF). The two pools are linked by the process of asymmetrical division within the self-renewing subset so that, at steady state of cellular replication in this TCR/CD27-dependent subset, one daughter cell remains undifferentiated and the other initiates its commitment to IL-2-dependent terminal differentiation. Superimposed on this basic scheme are a shift in the CD8(+) T cell response to type I and II interferon (IFN) from anti- to pro-proliferative and transcriptional control of replicative senescence by Bmi-1, Blimp-1, and BCL6/BCL6b. This developmental program ensures that despite the occurrence of cellular senescence antiviral CD8(+) T cell clones are maintained for the duration of persistent viral infections.
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PMID:The expansion and maintenance of antigen-selected CD8(+) T cell clones. 1798 Dec 5

The antigen-presenting molecules CD1 and MHC class I-related protein (MR1) display lipids and small molecules to T cells. The antigen display platforms in the four CD1 proteins are laterally asymmetrical, so that the T cell receptor (TCR)-binding surfaces are comprised of roofs and portals, rather than the long grooves seen in the MHC antigen-presenting molecules. TCRs can bind CD1 proteins with left-sided or right-sided footprints, creating unexpected modes of antigen recognition. The use of tetramers of human CD1a, CD1b, CD1c or MR1 proteins now allows detailed analysis of the human T cell repertoire, which has revealed new invariant TCRs that bind CD1b molecules and are different from those that define natural killer T cells and mucosal-associated invariant T cells.
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PMID:Lipid and small-molecule display by CD1 and MR1. 2638 32