The activating receptor that competes with TIGIT for CD155 binding–the balance determines T cell fate.
CD226 and TIGIT represent a classic activating-inhibitory receptor pair, analogous to CD28/CTLA-4. Both bind CD155Loading..., but with opposite functional outcomes. TIGIT has higher affinity, so when CD155 is abundant (as in tumors), TIGIT-mediated inhibition dominates.
This competition explains why simply measuring CD155 or TIGIT expression may be insufficient–the functional outcome depends on which receptor is engaged. FRET-based measurement could directly assess this.
Competing Receptors: CD226 and TIGIT both bind CD155, but have opposite effects. CD226 activates immune cells; TIGIT suppresses them.
The Balance Matters: Whether immune cells attack or stand down depends partly on which receptor "wins" the competition for CD155 binding.
Anti-TIGIT/CD155Loading...|TIGIT}} antibodies aim to block the inhibitory signal, shifting the balance toward CD226-mediated activation. Clinical trials combining anti-TIGIT with anti-PD-1 are ongoing.
CD226 itself can be downregulated on exhausted T cells, contributing to dysfunction. Measuring the CD226/TIGIT ratio and their respective engagement states could predict which patients will benefit from TIGIT blockade.
Drug Development: Anti-TIGIT drugs aim to block the suppressive interaction, allowing CD226 to dominate.
Patient Selection: Measuring which interaction predominates could potentially identify patients most likely to benefit from TIGIT-targeted therapy.
Theoretical Application: CD226 competes with TIGIT for CD155 binding, creating an immune activation/suppression balance. QF-Pro could potentially measure both CD226/CD155 and TIGIT/CD155 interactions, providing functional insight into net immune regulatory state.
Status: Theoretical application. Dual-target measurement could provide unique biological insight.
Future potential: CD226 is the "activating" receptor competing with TIGIT. Measuring both interactions simultaneously could reveal the net immune regulatory state in individual tumors.
