CD4+ T cells are critical regulators of health and disease. Defects in T cell function can result in a variety of immune disorders including susceptibility to infectious pathogens and the development of autoimmunity. In addition, T cell modulation of B cell responses is indispensable for establishing protective memory responses. T cell receptor (TCR) recognition of peptide-MHC (pMHC) is an essential first step in the induction of an immune response. Recent work has demonstrated a role for the strength of TCR interactions with pMHC in the induction of asymmetric cell division, whereby one parent cell gives rise to two daughter cells with differential cell fates. In this project we will study the contribution of TCR affinity to heterogeneous CD4+ T cell differentiation following either infection or immunization. We will focus on understanding the specific mechanisms and functional outcome of asymmetric division in CD4+ T cells. Defining the rules of CD4+ T cell differentiation may provide a rational basis for the design of safe and effective vaccines.