The evolution of investment in innate-like and diversified T cell receptors across development

Abstract

New insights into the diversity of lymphocyte functions challenges previous dogma about the rigid divide between innate and adaptive immunity. While T cells with canonically diversified receptors are crucial for recognizing novel antigens, other T cell lineages express innate-like receptors that recognize conserved molecular patterns. The relative frequency of innate-like to diversifying T cell receptors (iTCRs: dTCRs) varies greatly across vertebrate species and across ontogeny within species. These within-species dynamics can potentially be explained by developmental constraints on immunity, pathogen diversity and exposure, or by trade-offs associated with specificity. To better understand how these factors shape T cell repertoires, we constructed an agent-based model of TCR evolution inspired by the diversity of ontogenic life histories in amphibians but applicable to an array of vertebrate species. Our model features two life stages with distinct parasite populations and life history costs. The model predicts that changes in ontogeny (stage duration, T cell maturation time) and environmental factors (parasite diversity, parasite complexity) exert drastic effects on the stage structure of T cell investment strategies. A better understanding of the evolutionary pressures that shape TCR diversity will provide new insights into lymphocyte evolution and immune investment across organismal development.