Aim 1: Dissect the role of antigen affinity on TCR signaling and early T cell differentiation.  We have shown that CD4+ T cells responding during an infection can discriminate between antigen affinity and antigen dose, resulting in distinct types of effector and memory cell generation.  In this aim we will examine the effect of antigen affinity and dose on the activation, accumulation and subcellular localization of proximal and distal TCR signaling components.  Our goal is to clarify the molecular mechanisms behind segregation of TCR induced responses.

Aim 2: Investigate the contribution of of asymmetric division to CD4+ T cell differentiation.  One way that heterogeneous T cell fates can be achieved is through asymmetric cell division.  The experiments in this aim intend to elucidate if and how TCR affinity defines a threshold for asymmetric division in CD4+ T cells.

Aim 3: How do regulatory T cells (Tregs) modulate effector T cell responses during infection? Our preliminary data indicate a role for Tregs in the balanced differentiation of polyclonal CD4+ effector T cells during infection. The experiments in this aim will assess the efficacy and impact of Treg suppression on high versus low affinity activated T cells.