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D C Wraith

Publications and source records attributed to D C Wraith.

67 records · Page 4Linked to original sources
PubMed1988

Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention.

Experimental allergic encephalomyelitis (EAE) is an induced autoimmune disease mediated by CD4+ T lymphocytes. Analysis of T cell receptors of myelin basic protein-specific encephalitogenic T cell clones derived from six different PL/J (H-2u) or (PL/J x SJL) F1 (H-2uxs) mice revealed a limited heterogeneity in primary structure. In vivo, the majority of T lymphocytes recognize the N-terminal MBP-nonapeptide in association with I-Au and utilize the V beta 8 gene element. cDNA-sequencing showed that all T cell receptors from a panel of such T cell clones, grown in vitro, share the same V alpha gene segment. Despite heterogeneity in the D-J regions, the clones unexpectedly display a striking similarity in fine specificity. Based on these results, prevention and reversal of autoimmune disease with V beta 8-specific monoclonal antibodies was achieved.

Amino Acid Sequence↗
PubMed1987

Purified influenza virus nucleoprotein protects mice from lethal infection.

Local administration of nucleoprotein purified from X31 (H3N2) influenza A virus primed for A virus cross-reactive cytotoxic T cells and resulted in substantial protection (75%) of mice from a lethal challenge with the heterologous mouse-adapted A/PR/8/34 (H1N1) virus. By following the course of a lethal virus challenge we found that nucleoprotein priming did not prevent virus infection but rather aided recovery. Nucleoprotein-primed mice suffered initial symptoms of infection, i.e. weight loss and surface temperature changes, but started to recover after approximately 7 days. We suggest that such heterotypic protection can be attributed to priming of A virus cross-reactive cytotoxic T cells.

Animals↗
PubMed1986

Influenza virus-specific cytotoxic T-cell recognition: stimulation of nucleoprotein-specific clones with intact antigen.

The present study was undertaken to investigate the role of 'antigen processing' in influenza virus-specific cytotoxic T (Tc)-cell recognition. H-2 Db-restricted Tc-cell clones specific for the 1934 influenza nucleoprotein (NP) were tested in an in vitro proliferation assay for the recognition of intact virus, purified protein or peptide antigen. Inactivated virus required further 'processing', which was inhibited by either NH4Cl treatment or paraformaldehyde fixation of antigen-presenting cells (APC). Purified NP, by contrast, was readily presented by both normal peritoneal exudate cells and H-2 Db gene 'transfected' L cells. The response was not inhibited by either NH4Cl or prior paraformaldehyde treatment of APC. Peptone-induced peritoneal exudate cells presented ineffectively unless treated with NH4Cl or prefixed with paraformaldehyde. Comparison of the responses to either purified protein or a synthetic peptide implies that the epitope recognized by the three NP specific clones is not 'cryptic' and, therefore, that the purified protein, in this case, does not require 'processing'.

Ammonium Chloride↗
PubMed1985

Induction of influenza A virus cross-reactive cytotoxic T cells by a nucleoprotein/haemagglutinin preparation.

An ammonium deoxycholate fraction from bromelain-treated influenza A virus was highly enriched for virus nucleoprotein and contained residual haemagglutinin (NP/HA). The preparation did not contain detectable levels of matrix or neuraminidase proteins and was free of infectious virus. NP/HA effectively primed mice for cytotoxic T cells which lysed syngeneic cells infected with any type A influenza virus. Furthermore, NP/HA generated A-type virus cross-reactive cytotoxic T cells when added in vitro to spleen cells from mice previously primed with infectious influenza A virus. These properties imply that NP/HA has potential as a vaccine for heterotypic influenza A immunity.

Animals↗
PubMed1985

Control of immune interferon release by cytotoxic T-cell clones specific for influenza.

We have studied the release of immune interferon (IFN-gamma) by influenza-specific cytotoxic T-cell (Tc) clones. IFN-gamma release is entirely dependent on specific antigen recognition or mitogen treatment and correlates inversely with the growth rate of the clone, while no differences in cytotoxic activity can be discerned at the different stages of Tc maturation. Although the mitogen Con A provides a more powerful stimulus for IFN release by Tc clones, specific antigen leads to a more rapid secretion, starting within 2 hr of contact with Tc clones and their specific targets. This may be of significance in an infection, providing a quick, but localized, mechanism to prevent viral spread. We also examined whether ligand interactions with T-cell surface glycoproteins Lyt-2 or LFA-1, important in Tc recognition, affected IFN release. Monoclonal antibodies to both Lyt-2 and LFA-1 block specific target cell lysis of Tc clone BA4, but do not affect Tc clone T9/5. This latter finding adds LFA-1 to the list of T-cell surface components which are not always essential for target cell recognition. Antibody to Lyt-2 blocked antigen-induced IFN-gamma release by all Tc clones studied, whilst two monoclonal antibodies to LFA-1 had little or no effect. Thus, the Lyt-2 molecule plays a role in the regulation of IFN secretion.

Animals↗
PubMed1984

Dk-restricted antiinfluenza cytotoxic T-cell clone loses one of its two alloreactivities.

K6, an influenza-specific cytotoxic T (Tc)-cell clone derived from C3H/He mice, was Dk-restricted. Further analysis showed that K6 also recognized Dd and Dq as allotargets. The clonal nature of the three recognition specificities was confirmed by cold-target cell inhibition. After extensive in vitro selection, K6 lost the ability to lyse Dd cells while retaining both other specificities. The role of the Lyt-2 molecule in antigen-specific self-H-2-restricted vs allospecific recognition was investigated by inhibition with the Lyt-2-specific monoclonal antibody 53-6.7. Both activities were proportionately inhibited, indicating that the Lyt-2 molecule is equally important for both recognition specificities of this Tc-cell clone.

Animals↗
PubMed1983

Loss of serological determinants does not affect recognition of H-2Kk target cells by an influenza-specific cytotoxic T cell clone.

The recognition of "self determinants" by an H-2Kk-restricted cytotoxic T (Tc) cell clone (K5) has been investigated as follows: (a) differential inhibition of cytotoxicity by several monoclonal antibodies directed to determinants on the H-2Kk molecule of the target cells and (b) recognition and lysis of target cell variants of cell line LDHB, which have lost the majority or all of the serological determinants defined by the inhibiting antibodies while still expressing an H-2Kk molecule. Such variant cells infected with influenza virus were effectively recognized by Tc cell clone K5, whereas a target cell line, which lacks the Kk molecule, was not lysed. The results suggest; (a) that virus-specific Tc cell see "self" in a manner distinct from the recognition of serological determinants by B cell and (b) that antibody inhibition indicates conformational closeness, but not identity, of the class I determinant seen by T cells.

Animals↗
PubMed1982

Cell-surface remodelling during mammalian erythropoiesis.

Current evidence suggests that the major cell-surface modification occurring during mammalian erythropoiesis could be generated by two separate mechanisms: either selective loss of membrane proteins during enucleation or endocytosis at the subsequent reticulocyte and erythrocyte stages. The former idea was tested by collecting developing rabbit erythroid cells before and after the enucleation step and comparing their cell-surface protein composition via radiolabelling and electrophoresis. Few changes were observed. Our data thus lend support to the endocytosis mechanism.

Animals↗