Target Discovery and Validation Reviews and Protocols

296 Sioud
Fig. 10. Critical molecules involved in the interaction between the T-cells and the
antigen-presenting cells. The first signal consists of the T-cell receptor (TCR)–peptide–
MHC interaction. The second co-stimulatory signal resulting from the interaction between
CD28 and B7 molecules, leading to the amplification of the signaling process in naive
T-cells and protects activated cells from death. In absence of signal 2, T-cell activation will
lead to anergy. Several inducible costimulatory molecules, in particular CTLA4, negatively
modulate activation of T-cells. Notably, all of the constitutively expressed co-stimulators
have positive amplifying effects, whereas the group of inducible costimulators contains
positive (e.g., inducible co-stimulatory [ICOS]) and negative (e.g., CTL4 and PD-1) regulators.
APC, antigen-presenting cell.