The induction of protective immunity relies on immunological memory i.e. the ability of the immune system to respond more efficiently to a secondary antigenic chalenge. The capacity to recognize previously encountered antigens is retained over long periods and affects B and T lymphocyte populations. In this study, mice expressing a transgenic TCR which recognizes a peptide from influenza virus nucleoprotein presented on H-2 ClassI Db molecules will be used to study phenotypic and functional properties of memory CD8+ cytotoxic T cells. To follow activated CD8+ T cells over long periods,we will establish a method of labelling cells in vivo with a replication defective retrovirus which carries a B-Gal reporter gene. Phenotypic characterisation will include expression of membrane molecules which could be involved in long term survival of memory CD8 T cells. Functional analysis will be focussed on TCR signalling (regulation of intracellular calcium levels and activation of tyrosine kinases) as well as antigen dependant cytolytic activity and proliferation. To identify the mechanisms responsible for long term survival of memory CD8 T cells, expression of bc1-2 family survival genes as well as cytokine genes will be investigated.