The gamma delta T-cell receptors (TCRs) are limited in their diversity, suggesting that their natural ligands may be few in number. Ligands for gamma delta TCRs that have thus far been determined are predominantly of host rather than foreign origin. Correlations have been noted between the V gamma and/or V delta genes a gamma delta T cell expresses and its functional role. The reason for these correlations is not yet known, but several different mechanisms are conceivable. One possibility is that interactions between particular TCR-V domains and ligands determine function or functional development. However, a recent study showed that at least for one ligand, receptor specificity is determined by the complementarity-determining region 3 (CDR3) component of the TCR-delta chain, regardless of the V gamma and/or V delta. To determine what is required in the TCR for other specificities and to test whether recognition of certain ligands is connected to cell function, more gamma delta TCR ligands must be defined. The use of recombinant soluble versions of gamma delta TCRs appears to be a promising approach to finding new ligands, and recent results using this method are reviewed.
