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D O White

Publications and source records attributed to D O White.

At least 37 records · Page 2Linked to original sources
PubMed1985

Conformational changes in influenza virus haemagglutinin and its monomer detected by monoclonal antibodies.

Exposure of influenza virus haemagglutinin to pH 5 results in conformational changes occurring in the molecule which are accompanied by antigenic modifications. Furthermore, isolated haemagglutinin (HA) at a concentration of 0.1 nM undergoes dissociation from the trimeric to a monomeric form when exposed to pH 5. Whether present on intact virus or as the isolated monomer, each form of haemagglutinin from pH 5 exhibits similar alterations in antigenic characteristics. These forms of HA show modifications in the antigenic sites located in the hinge (site C), tip (site B) and subunit interface (site D) regions. Whereas binding of monoclonal antibodies recognizing the tip and interface is abrogated or diminished, binding of antibodies to the hinge region is greatly enhanced following exposure of virus or the monomeric form of HA to pH 5.

Antibodies, Monoclonal↗
PubMed1985

Mitogenic activity of influenza virus and haemagglutinin.

Influenza A viruses behave as T cell-independent B cell mitogens in vitro. The magnitude of the proliferation induced varies with the haemagglutinin subtype of the virus, the order being H2 greater than H6 greater than H3 greater than H1 for Balb/c mice. H3 viruses are equally mitogenic for all strains of mice tested. In contrast, the mitogenic response to H2 and H6 viruses is controlled by the I-E subregion of the major histocompatibility complex. These viruses are mitogenic only for strains of mice that express surface I-E antigen (haplotypes a, d, k, p, r), and not for haplotypes b, f, q, s, which fail to synthesize a normal E alpha chain and do not express surface I-E antigen. Mitogenesis by H2 and H6 viruses may involve direct interaction of virus with I-E molecules on the B lymphocyte or an accessory cell, whereas mitogenesis by H3 viruses does not appear to involve I-E.

Animals↗
PubMed1985

Murine helper T lymphocyte response to influenza virus: recognition of haemagglutinin by subtype-specific and cross-reactive T cell clones.

Helper T cel lines specific for influenza virus were established by continuous culture of Mem 71-Bel (H3) virus-immune spleen cells in the presence of virus and antigen-presenting cells and their specificity assessed in proliferation experiments. A line stimulated in vitro with Mem 71-Bel virus was able to proliferate in response to viruses of the same, and also of different, type A haemagglutinin (HA) subtypes as the immunizing virus but not to a type B influenza virus. A component of this cross-reactivity was due to recognition of the HA molecule. Lines stimulated in vitro with purified disrupted H3 or H2 viruses showed a higher degree of cross-reactivity. Of nine clones isolated from these lines, seven were directed against the HA molecule and recognized the HA1 chain. The HA-specific T cell clones were either subtype-specific T cell clones were either subtype-specific, recognizing only viruses of the H3 subtype, or cross-reactive, also recognizing viruses of the H2 subtype of type A (but not type B). Subtype-specific and cross-reactive T cell clones were shown to function as helper T cells in vitro. In addition to collaborating with H3 virus-primed B cells responding to H3 virus in culture, the cross-reactive T cell clone could also provide help for H2 virus-primed B cells making anti-HA antibody in response to H2 virus.

Animals↗
PubMed1985

Antibodies elicited by influenza virus hemagglutinin fail to bind to synthetic peptides representing putative antigenic sites.

A number of peptides of the hemagglutinin (HA) of X-31 influenza virus have been synthesised. The amino acid sequences of some of these peptides represent regions of HA which have been postulated [Wiley et al., Nature, Lond. 289, 373-378 (1981)] to form the antigenic sites of this molecule. Animals were immunized with free peptide or peptide conjugated to a carrier and the resulting antisera examined for their capacities to bind to homologous peptide, whole HA, reduced and alkylated HA, and intact virus. Not all peptides examined in this way were immunogenic. Only antibodies raised against the C-terminus of HA1 peptide displayed binding to virus. This antiserum bound to the intact HA but not to the reduced and alkylated form of the molecule. These results raise questions as to the feasibility of using synthetic peptides of the influenza HA in short linear sequences to elicit neutralising antibody.

Amino Acid Sequence↗
PubMed1985

Recognition of influenza virus hemagglutinin by subtype-specific and cross-reactive proliferative T cells: contribution of HA1 and HA2 polypeptide chains.

The recognition of influenza virus hemagglutinin (HA) by T lymphocytes was examined by assaying the T cell proliferative response of influenza virus-primed T cells to purified HA of different influenza A subtypes or to isolated heavy (HA1) or light (HA2) polypeptide chains of the HA molecule. The proliferative response to HA was dependent on the activation of an Ly-1+2- subset of T cells and required the presence of nylon wool-adherent, radiation-resistant accessory cells. T cells from mice primed by infection with one strain of type A influenza virus cross-reacted with other purified HA not only of the same subtype as the priming virus but also of serologically distinct subtypes of influenza A (but not B) virus. The response of virus-primed T cells to the homologous HA or to HA of the same subtype was shown to involve recognition of determinants on both the HA1 and the HA2 chains. The recognition of HA of different subtype by cross-reactive T cells appeared to be directed predominantly to determinants on HA2. Because the antibody response to influenza virus HA is not cross-reactive between subtypes and is directed predominantly to determinants on HA1, the present results indicate that at least some of the determinants on HA recognized by T cells are different from those recognized by B cells and that the HA2 chain may be involved primarily in stimulation of T cell rather than B cell immunity.

Animals↗
PubMed1984

Antiviral chemotherapy.

Progress in antiviral chemotherapy has taken place as a logical strategy for the design of antiviral agents has emerged. The second-generation nucleoside analogues, led by acyclovir, have proved their worth against herpesviruses and should now become a standard part of medical practice. Meanwhile, recombinant DNA technology has lowered the cost of interferons to the point at which the several human subtypes of these naturally occurring hormones can be subjected individually to controlled clinical trials against the viral diseases in the treatment of which they show promise. Yet, optimism about the future of antiviral chemotherapy must be tempered by the observation that most of the agents discussed in this review are described more accurately as promising rather than proven, and several of these have not yet been released in Australia at the time of writing.

Acyclovir↗
PubMed1984

Macrophages bind directly to Semliki Forest virus-infected cells and mediate antibody-dependent cell-mediated cytotoxicity.

Macrophages were found to bind directly to Semliki Forest virus (SFV)-infected, but not uninfected, P815 cells. In the presence of anti-H-2d or anti-BALB/c antibody, macrophages lysed SFV-infected, but not uninfected, P815 cells. It is proposed that macrophage-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) proceeds via two functionally distinguishable initial steps: (1) adhesion of effector to target cell, which may be mediated through antibody or through viral protein, as in the case of SFV-infected target cells suboptimally sensitized with antibody; (2) antibody-dependent initiation of cytolysis.

Animals↗
PubMed1984

Influenza viruses are T cell-independent B cell mitogens.

UV-inactivated influenza virus A strains of subtypes H1, H2, H3, and H6 were shown to be mitogenic for unprimed splenic lymphocytes from BALB/c mice. Representative viruses of these four subtypes all behaved as T cell-independent B cell mitogens. The magnitude of the proliferative response was determined by the subtype of the hemagglutinin molecule: H2 and H6 viruses were the most potent mitogens, and H3 viruses were moderately mitogenic, whereas H1 viruses induced only low, but significant, levels of proliferation. Mitogenesis was inhibited by antiviral sera and by monoclonal antibodies directed against hemagglutinin.

Animals↗
PubMed1982

Enumeration of antigenic sites of influenza virus hemagglutinin.

The antigenic sites on the hemagglutinin of X-31 (H3) influenza virus have been defined by using a competitive radioimmunoassay with a panel of monoclonal antibodies which includes those known to select variants with substitutions of particular amino acids. The capacity of each monoclonal antibody to block the binding of other radioiodinated monoclones to purified hemagglutinin permitted classification of the panel into four separate groups, each of which defined a particular antigenic site on the hemagglutinin molecule. Three of these are located on the polypeptide backbone and correspond to the "hinge," the "loop," and the "tip/interface" of the X-ray crystallographic model of Wiley et al. (Nature [London] 289:373-378, 1981). Nonreciprocal blocking of certain anti-interface antibodies by anti-loop antibody suggests that much of the exposed surface of the head of the hemagglutinin molecule extending from the loop to the interface may be a continuum of epitopes. A fourth antigenic site is carbohydrate in nature, presumably situated on the antigenic oligosaccharide side chains. These four domains are in addition to two antigenic sites defined by monoclonal antibodies that inhibit neither hemagglutination nor infectivity (Breschkin et al., Virology 113:130-140, 1981;' Yewdell et al., Nature [London] 279:246-248, 1979).

Antibodies, Monoclonal↗
PubMed1981

Antigenic determinants of influenza virus haemagglutinin. VI. Antigenic characterization of the oligosaccharide sidechains form HA1 of influenza virus haemagglutinins.

The oligosaccharide sidechains attached to the major polypeptide, HA1 of the haemagglutinin of influenza virus were examined for antigenic activity using a solid-phase radioimmunoassay. Cross-reactivity between the HA1 of the different human subtypes was clearly demonstrable with IgG raised against purified virus but was abrogated if anti-carbohydrate antibodies were first removed by passage of the IgG through an immunoadsorbent column containing haemagglutinin (HA) from an unrelated avian influenza strain. Antibodies eluted from the column were found to cross-react with the HA1 of all subtypes tested. 'Host antigen' extracted from chick chorioallantoic membrane and coupled to Sepharose was also able to remove cross-reactive antibodies from antiviral sera, while antibodies raised against host antigen bound to the HA1 isolated from each subtype tested. It is concluded that, although there are qualitative and quantitative differences between the oligosaccharide sidechains of influenza haemagglutinins, the antigenically active sidechains are cross-reactive.

Cross Reactions↗
PubMed1981

In vitro antibody response to influenza virus. II. Specificity of helper T cell recognizing hemagglutinin.

Intraperitoneal immunization of mice with liver influenza virus was shown to induce helper T (TH) cells with specificity for the hemagglutinin (HA). The interaction of virus-primed TH cells with purified HA was studied independently of B cell reactivity to the same antigen by using the generation of nonspecific help as an index of activation of HA-specific TH cells. TH cells from mice primed with any of the H3 viruses A/Aichi/68 X A/Bel/42 (H3N1), A/Memphis/102/72 X A/Bel/42 (H3N1) or A/Port Chalmers/73 (H3N2) were strongly cross-reactive towards HA of other strains within the H3 subtype. In addition, several examples of cross-reactivity towards HA of a different subtype were observed, usually of a lower magnitude. TH cells from mice primed to any of the H3 viruses above or to A/Bel/42 (H1N1) virus cross-reacted with the HA of A/Japan/305/57 (H2); furthermore, priming with A/Bel/42 or with A/Jap/305/57 X A/Bel/42 (h2N1) virus yielded TH cells that cross-reacted with certain of the H3 HA preparations. The cross-reactivity observed between subtypes was not due to the common chicken host carbohydrate component of HA, since no response to the purified type A HA preparations was obtained with T cells from mice primed with egg-grown influenza B/Hong-Kong/8/73 virus. The results indicate that HA of different subtypes may share cross-reactive antigenic determinants recognized by TH cells. Within a subtype, HA are highly cross-reactive with respect to tH cell recognition.

Animals↗
PubMed1980

Further characterization of natural killer cells induced by Kunjin virus.

The natural killer (NK) cell induced one to two days after Kunjin virus infection of BALB/c mice is cytotoxic for a wide range of syngeneic, allogeneic and xenogeneic cell lines. It is also weakly cytotoxic for some non-malignant cells including mouse fibroblasts, macrophages and thymocytes, but not lymph node cells. Levels of lysis of non-tumour target cells are dependent on their genotype. Furthermore, malignant cell lines may become resistant following transplantation in vivo then susceptible again after culture in vitro. The virus-induced NK cell is elicited as readily in athymic (nude) as in normal mice. X-irradiation inhibits its development if administered prior to infection. It is labile on culture at 37 degrees. The cell carries Fc receptors but its NK activity is not antibody-dependent.

Animals↗