Antigen-restricted γδ T-cell receptors?

Abstract

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.

γδ-T cells: an unpolished sword in human anti-infection immunity

“…91 However, care should be taken when identifying 'antigen-specific cd-T cells' before clarifying whether these 'memory-like responses' are antigen-restricted or presenting molecule-restricted. 92 For example, the CD1d agonist aGalCer can independently induce interferon (IFN)-c production by cd-T cells regardless of the presenting capability of CD1d, 93 which does not classically belong as an antigen-specific immune response.…”

Diversity of γδ T-cell antigens

“…However, it remains possible that cd TCRs have inherent biases for the recognition of cell surface molecules other than MHC, 23 and given the limitation of the repertoire outside of CDR3d, this even seems likely. 24 No such bias or restricting element has been firmly established, however. Perhaps the biggest difference to Ag recognition via BCRs is that so many conventional Ags seem to be incapable of eliciting responses by cd T cells.…”

“…It seems likely that this particular restriction of variability holds a clue that might eventually help to explain the Ag preferences of cd T cells. 24 …”

Rapamycin enhances IFN-γ and IL-4 production in co-culture of gδ T and dendritic cells from mice with lipopolysaccharide-induced acute lung injury

“…Dendritic cells (DCs) are the most important antigen-presenting cells of the mammalian immune system, which bridges the innate and the adaptive immune systems (Holtmeier and Kabelitz, 2005). DCs and gδ T cells have been reported to interact with each other either via TCRs or regulatory secreted cytokines (Born and O'Brien, 2009;Davey et al, 2014). For example, in Streptococcus pneumoniae-induced inflammation, gδ T cells can resolve inflammation by regulating DCs and macrophages (Davey et al, 2014).…”