Antigen recognition determinants of γδ T cell receptors

The molecular basis of gamma delta T cell receptor (TCR) recognition is poorly understood. Here, we analyze the TCR sequences of a natural gamma delta T cell population specific for the major histocompatibility complex class Ib molecule T22. We find that T22 recognition correlates strongly with a somatically recombined TCR delta complementarity-determining region 3 (CDR3) motif derived from germ line-encoded residues. Sequence diversity around these residues modulates TCR ligand-binding affinities, whereas V gene usage correlates mainly with tissue origin. These results show how an antigen-specific gamma delta TCR repertoire can be generated at a high frequency and suggest that gamma delta T cells recognize a limited number of antigens.