Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells.

Tissue-resident memory CD8 T cells (T) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of T cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to T cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector. We found that CD8 T cells of different specificities underwent antigen-dependent competition in the infected tissue, which shaped the composition of the local pool of T cells. This local cross-competition was active for T cells recognizing antigens that are coexpressed by infected cells. In contrast, T cell development remained largely undisturbed by the presence of potential competitors when antigens expressed in the same tissue were segregated through infection with antigenically distinct viral quasispecies. Functionally, local cross-competition might serve as a gatekeeping mechanism to regulate access to the resident memory niche and to fine-tune the local repertoire of antiviral T cells.