Abstract T-cells play major functions to combat infectious diseases and cancer, are critical for the effectiveness of vaccines, and may have negative effects in various types of immune disorders. While many of the genes involved in T-cell responses have been identified, it is likely that many remain unknown. The discovery of these genes and their specific roles during in vivo immune responses could provide major advances in our understanding of the immune system and for the improvement of vaccines and/or treatment of infectious diseases, cancer, and various immune disorders. Here we propose to generate mice with T-cell deletions of genes whose transcription is perturbed in specific T-cell populations during protective anti-viral T-cell responses. Our hypothesis is that some of these genes will play essential roles in immune responses to pathogens and possible in cancer and various immune dysfunctions. The mouse models developed through this grant will provide new valuable information about the role of still little-known genes in the modulation of the anti-viral immune response and resistance to viral infection and may be the basis of future novel discoveries encompassing not only immunology but other areas of mammalian biology.