Fas receptor (CD95) and Fas ligand (CD178) interaction (Fas/FasL veto interaction)

The Fas–FasL-mediated veto interaction is a specialized immunological mechanism used to induce antigen-specific tolerance, particularly in the context of hematopoietic stem cell or organ transplantation (Reisner et al., 2011, Nature Reviews Immunology). In this process, a veto cell (such as a CD8+ T cell or a bone marrow-derived cell) expresses Fas ligand (FasL/CD178) (UniProt P48023). When an alloreactive host T cell recognizes the MHC-peptide complex on the veto cell via its T-cell receptor (TCR), the interaction triggers the expression of the Fas receptor (CD95) on the alloreactive T cell (UniProt P25445; Reich-Zeliger et al., 2000, Journal of Immunology). The subsequent binding of FasL on the veto cell to Fas on the T cell activates the extrinsic apoptotic pathway, leading to the selective deletion of the alloreactive T cell. This mechanism is a key target for therapeutic strategies aimed at preventing graft-versus-host disease (GvHD) and organ rejection by eliminating only the T cells that would attack the graft, while sparing the rest of the immune system. Drugs and cell therapies targeting this pathway, such as Asunercept (APG-101), aim to either enhance this veto effect to promote tolerance or inhibit it in conditions like cancer where Fas-mediated apoptosis of immune cells is detrimental (Apogenix).

Other names

Veto effectFas-mediated apoptosis of alloreactive T cellsCD95/CD178 interactionTNFRSF6/TNFSF6 interactionVeto cell interaction

Induction of apoptosis in alloreactive T cells through the activation of the Fas-mediated extrinsic apoptotic pathway upon TCR-mediated recognition of the veto cell.