Environmental and genetic factors shape the human T-cell receptor repertoire.

Both environmental and genetic factors combine to shape the TCR repertoire as measured by V gene usage. These factors may result in dramatic shifts in normal subjects, which cannot be discounted when studies are performed in patients with disease. Future studies need to explore further examples of genetic and environmental factors that shape the TCR repertoire to understand the full extent of variation in a normal population and the mechanisms involved. Some of these mechanisms may also apply to TCRG, TCRD, and immunoglobulin loci. Certainly variations in the efficiency of V(D)J rearrangement could affect any rearranging multigene locus. Eventually such studies will lead to better designed clinical studies of the repertoire in disease, through the selection of control populations matched for environmental exposure and genetic background. In this respect, family studies will be most useful.