CD43, a molecule defective in Wiskott-Aldrich syndrome, binds ICAM-1.

THE protein CD43 (also known as sialophorin, leukosialin, large sialoglycoprotein or gp115) is expressed on the surface of T lymphocytes, monocytes, neutrophils, platelets and some B lymphocytes. Expression of CD43 is deficient and/or defective in the X-chromosome-linked immunodeficiency disorder Wiscott-Aldrich syndrome, suggesting that CD43 might have a role in T-cell activation. We have shown that expression of human CD43 in an HLA-DR-specific murine T-cell hybridoma enhances the antigen-specific response to stimulation by the human lymphoblastoid cell line Daudi, and that Daudi cells bind specifically to purified immobilized CD43. These data indicate that the specific interaction of CD43 with a ligand on the surface of Daudi cells might contribute to T-cell activation. Here we report evidence that intercellular adhesion molecule-1 (ICAM-1, or CD54), is a ligand for CD43.     

HLA-restricted T-cell recognition of Epstein-Barr virus-infected B cells

In mice the cytotoxic T-cell response to several types of virus is influenced by genes within the major histocompatibility complex; in particular, genetic control is exercised at the effector cell level through a requirement that virus-specific cytotoxic T cells recognise viral antigens in association with H-2K and H=2D region gene products on the surface of infected cells. In man the restriction which the analogous HLA-A, -B and -C-region gene products might place on virus-specific T-cell function is still in dispute. The earliest and most controversial evidence concerns the Epstein-Barr virus (EBV), a B lymphotropic agent which causes infectious mononucleosis (IM) and which induces an unusually vigorous T-cell response; cytotoxic T cells from IM patients' blood were shown to be EBV-specific yet, in contrast to mouse systems, apparently free of any obvious HLA restriction. Since then T-cell recognition of EBV-infected B cells has assumed particular significance as a model system for the study of cytotoxic T-cell function in man. This report describes the results of a new approach clearly indicating that HLA-A and -B region products do indeed have a role in this system.     

The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro

Cell-free extracts prepared from human 293 cells, supplemented with purified SV40 large-T antigen, support replication of plasmids containing the SV40 origin of DNA replication. A cellular protein (Mr approximately 36,000) that is required for efficient SV40 DNA synthesis in vitro has been purified from these extracts. This protein is recognized by human autoantibodies and is identified as the cell-cycle regulated protein known as proliferating cell nuclear antigen (PCNA) or cyclin.     

Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes

The T-cell receptor (TCR) gamma polypeptide is expressed associated with CD3 (T3) on the surface of normal human peripheral blood lymphocytes. These cells function as non-MHC-restricted cytotoxic T lymphocytes (CTL)and thus may play an important role in host immune defence. The TCR gamma polypeptide occurs as a dimer in at least two molecular forms based on the absence or presence of disulphide linkage. These forms use TCR gamma polypeptides with strikingly different peptide backbone sizes.     

Failure of familial Alzheimer's disease to segregate with the A4-amyloid gene in several European families

The gene coding for the amyloid protein, a component of neuritic plaques found in brain tissue from patients with Alzheimer's disease, has been localized to chromosome 21, and neighbouring polymorphic DNA markers segregate with Alzheimer's disease in several large families. These data, and the association of Alzheimer's disease with Down's syndrome, suggest that overproduction of the amyloid protein, or production of an abnormal variant of the protein, may be the underlying pathological change causing Alzheimer's disease. We have identified a restriction fragment length polymorphism of the A4-amyloid gene, and find recombinants in two Alzheimer's disease families between Alzheimer's disease and the A4-amyloid locus. This demonstrates that the gene for plaque core A4-amyloid cannot be the locus of a defect causing Alzheimer's disease in these families. These data indicate that alterations in the plaque core amyloid gene cannot explain the molecular pathology for all cases of Alzheimer's disease.     

Retrograde transport by the microtubule-associated protein MAP 1C

Microtubules are involved in several forms of intracellular motility, including mitosis and organelle movement. Fast axonal transport is a highly ordered form of organelle motility that operates in both the anterograde (outwards from the cell body) and retrograde (from the periphery towards the cell body) direction. Similar microtubule-associated movement is observed in non-neuronal cells, and might be involved in secretion, endocytosis and the positioning of organelles within the cell. Kinesin is a mechanochemical protein that produces force along microtubules in an anterograde direction. We recently found that the brain microtubule-associated protein MAP 1C (ref. 7) is a microtubule-activated ATPase and, like kinesin, can translocate microtubules in an in vitro assay for microtubule-associated motility. MAP 1C seemed to be related to the ciliary and flagellar ATPase, dynein, which is thought to produce force in a direction opposite to that observed for kinesin. Here we report that MAP 1C, in fact, acts in a direction opposite to kinesin, and has the properties of a retrograde translocator.     

Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters

Excitatory amino acids mediate fast synaptic transmission in the central nervous system through the activation of at least three distinct ionotropic receptors: N-methyl-D-aspartate (NMDA), the alpha-amino-3-hydroxy-5-methyl-isoxasole-4-propionate (AMPA)/quisqualate (QUIS) and the kainate subtypes (for reviews, see refs 1, 2). They also activate the additional QUIS 'metabotropic' receptor (sensitive to trans-1-amino-cyclopentyl-1,3-dicarboxylate, ACPD) linked to inositol phospholipid metabolism. We have used hippocampal slice cultures to study the electrophysiological consequences of the metabotropic response. We find that activation of an ACPD-sensitive QUIS receptor produces a 'slow' excitation of CA3 pyramidal cells, resulting from depression of a Ca2(+)-dependent K+ current and a voltage-gated K+ current. Combined voltage-clamp and microfluorometric recordings show that, although these receptors can trigger an increase in intracellular Ca2+ concentration, suppression of K+ currents is independent of changes in intracellular Ca2+. These effects closely resemble those induced by activating muscarinic acetylcholine receptors in the same neurons and suggest that excitatory amino acids not only act as fast ionotropic transmitters but also as slow neuromodulatory transmitters.