Antigen Recognition Determinants of γδ T Cell Receptors

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Abstract
The molecular basis of γδ T cell receptor (TCR) recognition is poorly understood. Here, we analyze the TCR sequences of a natural γδ T cell population specific for the major histocompatibility complex class Ib molecule T22. We find that T22 recognition correlates strongly with a somatically recombined TCRδ 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 γδ TCR repertoire can be generated at a high frequency and suggest that γδ T cells recognize a limited number of antigens.