Depending on the type and the context of an antigenic challenge, the immune system dominantly invokes either a type 1 (cellular) or a type 2 (humoral) response, but not both. The switch between the two response types is believed to involve T1 and T2 cytokines, but cellular mechanisms and genetic control of this process are poorly understood. We have developed a method to elicit cytotoxic T lymphocytes (CTLs) by peptide/adjuvant immunization in vivo. These specific combination of the adjuvant used and optimal CTL epitome peptides uncovers a novel pathway of CTL stimulation. This pathway appears to use B cells as antigen-presenting cells (APCs). Furthermore, in certain mouse strains, this CTL response is under control of an lr gene (possibly a complement gene) which maps to the class III region of the major histocompatibility complex (MHC). CD4 T cells and a cytokine network are involved in this Lr control, confirming that we are studying a case of T1/T2 switching. Taking advantage of the unique features of our peptide/adjuvant immunization, we propose to investigate the role of T-B interaction in, and the class III Ir gene regulation of, T1/T2 switching. As CTL vaccination is an obviously attractive strategy in combating infectious diseases and cancer, the practical significance of the above basic studies is that they should allow us to manipulate the response switch to obtain CTL vaccines successful in outbred populations. We propose to 1. Elucidate cellular, cytokine and complement requirements for the class III Ir control of peptide/adjuvant priming of CTLs, and 2. Isolate and characterize the class III Ir gene which controls T-B interaction and CTL responses.
