Rolf M. Zinkernagel
University of Zurich
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Primary Section: 43, Immunology and Inflammation Secondary Section: 44, Microbial Biology Membership Type:
International Member
(elected 1996)
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Research Interests
In the past, I have studied the relationships between viruses and the host's immune system, particularly the specificity of T cells for the self-MHC-molecules and viral peptides, their positive selection in the thymus, deletion in the thymus, or exhaustion in the periphery and have studied the anti-viral protective effector mechanisms via perforin or interleukin. This protective immunity also may cause immunopathology dependent upon a variety viral (IFN susceptibility, replication time, tropism, cytopathogenicity) and host (MHC, IFN levels, etc.) parameters. If viral antigens are not expressed in lymphoid tissues, they are ignored by T cells as are most self antigens of solid peripheral organs. Present studies aim to define cytotoxic T cell memory and try to exhaust memory T cells as a possibility to inhibit T cell-mediated immunopathology. Recent studies in my lab on neutralizing antibodies responses against viruses have established that paracristalline repetitive antigens on viruses cross-link antibody receptors and induce B cells best, that neutralizing antibodies are of high affinity and do not increase affinity with time, and that B cells are not tolerant. Noncytopathic, but not cytopathic viruses can infect specific neutralizing, but not nonneutralizing B cells, which can be lysed by cytotoxic T cells. This explains the delay in neutralizing antibody responses seen in HBV and HIV infections. Ongoing experiments analyze the neutralizing antibody repertoire and somatic mutations, attempt at studying T helper cell receptor transgenic and anti-viral antibody transgenic mice with respect to immune responses and tolerance. The overall aims are to learn about basic and biologically relevant parameters of specificity, tolerance, and memory of the immune system to understand pathogenesis and prevention of infectious disease.
