IMMUNE RECOGNITION OF INFLUENZA HEMAGGLUTININ AS A VIRAL AND A NEO-SELF-ANTIGEN

To analyze mechanisms governing tolerance and autoimmunity to self-ant igens, we have generated lineages of transgenic mice that express the influenza virus PR8 hemagglutinin (HA) as a neo-self-antigen. By compa ring the HA-specific T and B cell responses that can be induced in HA Tg mice with those that are induced in non-Tg (BALB/c) mice, the speci ficity and genetic basis with which tolerance is induced to the HA has been examined. This article summarizes studies using lineages of HA T g mice that express different forms and amounts of the HA under the co ntrol of the SV40 promoter/enhancer. Our studies have revealed that sp ecific subsets of HA-specific T and B cells are negatively selected fr om the primary repertoires of HA Tg mice. However, substantial populat ions of HA-specific T and B cells evade negative selection and can be activated by virus immunization. Understanding the capacity of these a utoreactive lymphocytes to differentiate and participate in antigen-sp ecific immune responses will provide important insights into mechanism s by which autoimmunity might be induced by viruses bearing structural similarities with self-antigens.