(284e) How T Cells Hunt for Antigen in Lymphoid Tissue

Recent in vivo two-photon microscopy experiments show that the migration of T lymphocytes (T cells) in the lymph and spleen is characterized by trajectories that exhibit random walk statistics. This raises the question as to whether chemokines that provide attractive cues are important. We have developed a computational model that shows that the existence of short-range attractive forces between T cells and antigen presenting cells (APCs) is consistent with random walk statistics. This is justified based on the theory of diffusion in random media. We employ higher order correlation function to detect the presence of these short-ranged attractions in experimental data, and with our experimental collaborators, we have been able to shed light on situations where attractive cues are important. Our simulations also suggest that the optimal search strategy is stochastic repertoire searching with short-range attractions. We have also used the computational tools to study the lag time between the arrival of antigen in lymphoid tissue and activation and proliferation of the relevant T cell population. Lag times of the order of days are predicted for a wide variety of circumstances. These results suggest an explanation for why T cells are not efficient vaccines against SHIV infection.