Mounting successful immune responses with highly cross-reactive TCR: the role of regulatory T cells

Adaptive immunity has a large clonotype repertoire of lymphocytes characterized by a unique receptor to deal with the multitude of pathogens. Each lymphocyte receptor is estimated to have a high cross-reactivity but it may lead to autoimmune responses. For the self-non-self discrimination, lymphocytes undergo negative selection during their development. However, it has been reported that self-reactive lymphocytes still present in the periphery. Here, we hypothesized that a subset of T cells, regulatory T cells, helps a successful immune response that is difined as avoiding an autoimmune response but mounting an immune response against pathogens. By means of a probabilistic model, we calculate the probability of a successful immune response with certain cross-reactivity of T cells. In the realistic range of cross-reactivity, producing regulatory T cells becomes beneficial.