Recombination biases predispose T cell receptor clustering in antigen-specific repertoires

Adaptive immunity relies on the tiling of antigenic space by diverse receptors created by genetic recombination. How robust responses to an immune challenge across a population emerge from this random generation of receptors is poorly understood. Recent evidence points at T cell responses being largely supported by convergent sequence space clusters found across individuals, while also supporting loner T cell in sequence space isolation. In this talk I will show data to this effect and disentangle different statistical contributions to the shape of reacting T cell repertoires. I will show how the recombination statistics support the emergence of these clusters, while the interplay of selection can both increase it while also creating loner T cells. I will demonstrate these contributions both analytically and using computational models. Eventually I will show how these models can be used to analyze and predict shape space structure of responding repertoires, potentially useable to both basic understanding of the adaptive immune system and clinical applications.