MOLECULAR RECOGNITION OF ANTIGEN INVOLVES LATTICE FORMATION BETWEEN CD4, MHC CLASS-II AND TCR MOLECULES

Recent evidence indicates that CD4 stably binds to major histocompatib ility complex (MHC) class II only after assuming an oligomeric state: the membrane-distal CD4 D1-D2 module interacts directly with MHC class II, whereas the membrane-proximal CD4 D3-D4 module mediates oligomeri zation. This results in the formation of aggregates critical for T-cel l activation. The T-cell receptor (TCR) regulates specific crosslinkin g and is itself dependent on lattice formation to trigger physiologica l T-cell responses. Here, Toshiko Sakihama, Alex Smolyar and Ellis Rei nherz discuss the molecular nature of CD4-MHC class II clustering and how, despite each of the component interactions being of low affinity, the molecular matrix renders T-cell recognition extremely specific an d sensitive.