Peter C. DOHERTY

Department of Microbiology and Immunology, The University of Melbourne, Australia

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Title: Virus Killers and Killer T cells

A major challenge for those of us who are interested in minimizing the toll of infectious disease is that RNA viruses with poor genomic fidelity throw off large numbers of variants that emerge as viable escape mutants following immune selection. This is a particular problem for designing vaccines to combat the “killer” viruses that cause AIDS, hepatitis C and influenza, all of which are major causes of human morbidity and mortality. Of these, our greatest success has been with influenza, though it is necessary to maintain constant global surveillance and to design new vaccines annually. Considerable effort is being made via the multi-centre HIV/AIDS neutralizing antibody consortium to develop strategies for skewing B cell immunity towards more conserved, shared determinants, such as the binding site on the external HIV Env molecule that engages with the CD4 cell-surface receptor. If successful, there will be a big push to apply such approaches to other pathogens. In the meantime, it is the case that the “killer” cytotoxic T lymphocytes (CTLs) that are specific for virus peptides presented by self major histocompatibility complex class I (MHCI) glycoproteins tend to be directed at relatively conserved virus components. The nature of the effector and memory phases of CTL-mediated immunity will be discussed, together with the limitations and potential benefits of vaccines that emphasize this aspect of host responsiveness.