How much (immune) diversity is enough?

Adaptive immune systems face a delicate balance between maximizing recognition of pathogenic antigens that should be attacked while minimizing the amount of auto-immunity against self antigens. Vertebrate T cell immunity splits this recognition task between major histocompatibility (MHC) proteins and receptors on the surface of T cells (TCR). While MHC genetic diversity has been explored for decades, only recently have sequencing advances made TCR diversity accessible. We focus on data from the great apes to analyze phylogenetic and population genetic patterns of TCR germline evolution and examine within-individual TCR diversity jointly with MHC diversity to investigate their effect on each other. Remarkably, we see little evidence for selection at the population or phylogenetic levels in the great apes, and essentially no evidence for MHC affecting TCR diversity at the within-individual level, although we do see hints of intra-individual selection on individual TCRs. These findings prompt us to reexamine the larger questions of what drives these immune loci to be genomic outliers and how much immune diversity is actually enough?