Microbiology & Immunology - Research Publications

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    Coronavirus-like particles in adults in Melbourne, Australia.
    Marshall, JA ; Thompson, WL ; Gust, ID (Wiley, 1989-12)
    Coronavirus-like particle(s) (CVLP) are faecal-derived pleomorphic membrane bound virus-like particles characterised by a fringe of club-shaped spikes that measure about 27 nm in length. The association of CVLP with a variety of social, clinical, and epidemiological factors was examined after a 69 month survey of faeces received for routine testing at an infectious diseases hospital. CVLP was found most commonly in three groups: first, intellectually retarded individuals who were usually inmates of institutions; second, recent overseas travellers who were either Indochinese refugees/immigrants or were overseas travellers who had usually visited developing communities for lengthy periods; and, third, male homosexuals who had a history of multiple sexual contacts and/or venereal disease. It was concluded that the excretion of CVLP had a strong association with unhygienic living or working conditions irrespective of any clinical symptoms the individual might show.
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    SPECIES-RESTRICTED INTERACTIONS BETWEEN CD8 AND THE ALPHA-3 DOMAIN OF CLASS-I INFLUENCE THE MAGNITUDE OF THE XENOGENEIC RESPONSE
    IRWIN, MJ ; HEATH, WR ; SHERMAN, LA (ROCKEFELLER UNIV PRESS, 1989-10-01)
    As compared with the vigorous T cell response normally observed against allogeneic MHC molecules, T cells recognize xenogeneic MHC molecules poorly. To define structural features of the MHC molecule important for such species-specific recognition, HLA-A2(A2)-specific murine CTL were examined for their recognition of transfected cell lines expressing the class I molecules A2 or A2/H-2Kb(A2/Kb). A2/Kb is a chimeric molecule consisting of the alpha 1 and alpha 2 domains of A2 and the alpha 3, transmembrane, and cytoplasmic regions of Kb. The majority of CTL clones showed enhanced recognition of transfected cell lines expressing this chimeric molecule. Enhanced recognition was shown to correlate with sensitivity of the CTL clones to inhibition by anti-CD8 antibody. These results suggested that CD8 may interact with class I in a species-specific manner, and that suboptimal CD8 interaction with the alpha 3 domain of xenogeneic molecules may be an important contribution to poor xenoreactivity. This conclusion was supported by the capacity of A2/Kb, but not A2 human cell transfectants, to induce a primary in vitro CTL xenoresponse specific for A2.
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    Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization.
    Carbone, FR ; Bevan, MJ (Rockefeller University Press, 1989-03-01)
    CTL recognize peptide forms of processed, foreign antigens in association with class I molecules encoded by the MHC and are usually directed against endogenously synthesized "cellular antigens," such as those expressed by virus-infected cells. In vitro studies have shown that small exogenous peptides can directly associate with class I molecules on the cell surface and mimic the target complex derived by intracellular processing and presentation. We have recently generated OVA-specific, H-2Kb-restricted CTL by immunizing C57BL/6 mice with a syngeneic tumor line transfected with the OVA cDNA. The CTL recognize the OVA transfectant E.G7-OVA and the synthetic peptide OVA258-276, but fail to recognize the native protein. We reasoned that given the potential for direct peptide/class I association observed in vitro, OVA258-276 may induce CTL after in vivo priming. However, we found that this is not the case. OVA258-276 and peptides of increasing lengths up to OVA242-276 and OVA242-285, which are all able to form the target complex in vitro, are inefficient at priming E.G7-OVA-specific CTL responses after intravenous injection. This is also true for both native and denatured OVA. In contrast to these results the synthetic peptide OVA229-276 corresponding to a peptide in a partial tryptic digestion of OVA can efficiently prime C57BL/6 mice in vivo after intravenous injection. This peptide elicits CTL that appear identical to those derived from animals immunized with syngeneic cells producing OVA endogenously. These results are discussed in terms of separate class I and class II antigen presentation pathways and the ability of only certain, exogenous antigens to enter the cytoplasmic, class I pathway.