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Biomedical subjects

J K Larson

Publications and source records attributed to J K Larson.

11 recordsLinked to original sources
PubMed1992

Monoclonal antibody detection of a major self peptide. MHC class II complex.

MHC class I and class II molecules transport foreign and self peptides to the cell surface and present them to T lymphocytes. Detection of these peptide:MHC complexes has thus far been limited to analysis of the response of a T cell. Previously, we showed that a mAb, Y-Ae, reacts with 10 to 15% of class II molecules on peripheral B lymphocytes and on cells in the thymus medulla but not thymus cortex in mice that express both I-Ab and I-Eb molecules. Elsewhere, we show that Y-Ae detects a self E alpha peptide bound to I-Ab molecules. Data presented here suggest that the antibody binds over the peptide binding groove of class II molecules, and, like a TCR, appears to recognize both the self peptide and polymorphic class II residues. In addition to B lymphocytes, the Y-Ae determinant is expressed at comparable levels on other APC, including macrophages and dendritic cells. Finally, the antibody does not react with invariant chain-associated class II complexes, thus providing direct evidence that invariant chain:class II complexes and peptide:class II complexes are mutually exclusive. These data provide further evidence that immunologic self is of limited complexity, and have important implications for T cell selection, self tolerance, and autoreactivity.

Animals↗
PubMed1992

Immune response to the nominal phosphoprotein of rabies virus.

The immune response to the nominal phosphoprotein (NS protein) of rabies virus was investigated with the use of a vaccinia recombinant virus that expressed the NS protein of a fixed rabies virus strain. Mice of the H-2k haplotype that were injected with either live rabies virus or the vaccinia recombinant virus developed a strong cytolytic T-cell response specific for the NS protein. This response was under immune response (Ir) gene control. The NS protein as presented by the vaccinia recombinant virus was a poor inducer of rabies virus-specific T-helper (Th) cells and B cells in the H-2k background. Furthermore, mice of the H-2k haplotype could not be protected by vaccination with the vaccinia recombinant virus expressing the NS protein, although protection in outbred mice was partial and incomplete. These data indicate that cytolytic T cells to the NS protein of rabies virus are insufficient to protect mice against a challenge with rabies virus.

Animals↗
PubMed1992

Posttranslational side chain modification of a viral epitope results in diminished recognition by specific T cells.

A stretch of 16 amino acid residues within the nominal phosphoprotein of rabies virus was shown to carry an immunodominant epitope for class I- and class II-restricted T cells. The nominal phosphoprotein of rabies virus is thought to be heterogeneously phosphorylated at multiple serine and threonine residues. The synthetic peptide that expressed the T-cell epitope contained a single serine residue corresponding to position 196 of the protein. Phosphorylation of this serine within the synthetic peptide caused a significant decrease of the antigenic potency of the peptide. A similar effect was seen if the serine was replaced by an alanine or if the peptide was glycosylated at its acidic residues. These data suggest that T-cell-mediated recognition of antigen presented by major histocompatibility complex class I- or II-positive cells is impaired not only by point mutations but also by posttranslational side chain modifications of residues within viral epitopes.

Amino Acid Sequence↗
PubMed1991

Identification of an immunodominant epitope within the phosphoprotein of rabies virus that is recognized by both class I- and class II-restricted T cells.

Immunization of H-2k mice with live rabies virus induces cytolytic T lymphocytes to the phosphoprotein of rabies virus. The antigenic determinant responsible for stimulating this class I-restricted cytolytic response was mapped to 50 amino acids (residues 180 to 229) of the phosphoprotein by using vaccinia virus recombinants expressing either the full-length phosphoprotein or C-terminal truncations of the phosphoprotein. The epitope was more finely mapped to residues 191 to 206 by using synthetic peptides. Several CD4+, class II-restricted T-cell lines were isolated from splenocytes of H-2k mice immunized with the vaccinia virus-rabies virus phosphoprotein recombinant virus. These lines were specifically stimulated by the phosphoprotein, and in addition, each line proliferated and released lymphokines in response to the same synthetic peptide shown to stimulate phosphoprotein-specific, class I-restricted cytolytic T cells.

Amino Acid Sequence↗
PubMed1989

Induction of rabies virus-specific T-helper cells by synthetic peptides that carry dominant T-helper cell epitopes of the viral ribonucleoprotein.

The T-helper cell response to the internal proteins of rabies virus was investigated. The rabies virus nucleoprotein was shown to be a major target antigen for T-helper cells that cross-react between rabies and rabies-related viruses. T-helper cells were assayed in vitro by testing virus-induced lymphocytes for lymphokine secretion in response to antigen. Immunodominant T-helper cell epitopes of the viral nucleoprotein were identified in vitro by using synthetic peptides delineated from the amino acid sequence of the nucleoprotein. The response to synthetic peptides were under Ir gene control. Antigenic peptides were tested in vivo for stimulation of rabies virus-specific T-helper cells. Inoculation of mice with peptides bearing immunodominant T-helper cell epitopes resulted in an accelerated and enhanced neutralizing antibody response upon booster immunization with inactivated rabies virus.

Amino Acid Sequence↗
PubMed1984

Ultrastructural localization of specific gonococcal macromolecules with antibody-gold sphere immunological probes.

In an effort to determine the ultrastructural location of specific macromolecules on the surface of intact microorganisms and in experimentally infected tissues, a new method of rapidly conjugating antibodies to gold spheres via a staphylococcal protein A intermediary has been developed. This new technique provides the excellent density of marking and versatility of sphere size provided by existing gold methods, but decreases preparation time, decreases the chance of bacterial contamination of antibody reagents, and increases specificity of marking. Staphylococcal protein A-coated gold spheres were conjugated with antibodies from rabbits immunized with purified gonococcal pili. The resulting gold-antibody conjugates allowed demonstration of antibody binding to pilus structures of the same gonococcal strain whose pili were used to raise the antibody and demonstration of the lack of antibody recognition of pilus structures on two other gonococcal strains. The failure of gold spheres to attach to isogenic nonpiliated clones of the homologous gonococcus indicated the absence of pilus antigens on the surface of these organisms. The use of a double label--small gold spheres conjugated to anti-pilus antibody and larger gold spheres conjugated to anti-protein I antibody--allowed the simultaneous localization of two gonococcal antigens.

Antibodies, Bacterial↗
PubMed1982

Computer-assisted spirometry.

The largest change in spirometric pulmonary function testing in the last 10 years has been the introduction of the digital computer for data acquisition and reduction. Computer-assisted spirometry can enhance the effectiveness of spirometric testing by increasing test accuracy, increasing patient acceptance, and decreasing the time necessary to complete the test and its interpretation. Any computer-assisted spirometer should be easy to use and should clearly display and properly report test results. I recommend that the American Thoracic Society Standards for spirometric testing be used by pulmonary function laboratories and that test interpretation made by a computer be verified.

Diagnosis, Computer-Assisted↗
PubMedDate not supplied

The molecular biology of rabies viruses.

Comparative nucleotide and deduced amino acid sequence analyses of the RNA and proteins of several fixed rabies virus strains have allowed detailed characterization of structural-functional relations of individual virus components. Several unique features of rabies viruses have been deduced from the complete nucleotide sequences of four of the five genes and the four intergenic regions of the genome. The most extensively analyzed rabies virus gene has been that of the surface glycoprotein. Direct comparisons between the deduced amino acid sequences of glycoprotein variants have led to the location of specific sites on the glycoprotein that bind virus-neutralizing antibodies and to the identification of an epitope correlating with viral pathogenicity. Structural requirements for immunogenic activity within the glycoprotein have also been investigated. This article presents an overview of the molecular biology of rabies viruses and describes the current state of knowledge of immunobiologic characteristics of different rabies virus components.

Amino Acid Sequence↗
PubMedDate not supplied

Computer application in the pulmonary laboratory. Part 1. Selection.

Successful application of computers in the pulmonary laboratory depends on many factors. The question no longer seems to be whether to have a computer but how to apply it in the most effective manner. Three main steps are involved in the application process: part 1 will examine selection of the computer and of the tasks that it must perform, and part 2 will discuss programming and validation.

Decision Making↗