Antigen-restricted gammadelta T-cell receptors?

After more than two decades of investigation, the biological role of the gammadelta T-cell receptors (TCRs) remains elusive. In fact, a theory of ligand recognition is still lacking that accounts for their adaptable structure, their peripheral selection, and the observed responses of gammadelta T cells, which do not require immunization but only include cells sharing germline-encoded components of the TCR. Assuming that all gammadelta T cells recognize ligands by a common mechanism, we now propose that germline-encoded components of the gammadelta TCRs provide for the specific recognition of a select set of antigenic determinants (Ags) which appear on the cell surface in various molecular associations. Furthermore, we hypothesize that the adaptivity of the gammadelta TCRs serves to increase affinity for the molecules with which these Ags associate rather than for the Ags themselves. Here we outline this hypothetical mechanism and discuss its possible implications for thymic selection and potential for complementing known innate and adaptive mechanisms of immune defense.