Simplified scheme of T cell activation by A) the T cell receptor and the co-stimulatory receptor, CD28 and B) a chimeric receptor in which co-stimulation and antigen specific activation are provided by a single molecule that is not dependent on MHC-1-associated peptide presentation. *LCK is a lipid raft-associated protein that phosphorylates ITAMs of the TCR zeta chain, allowing them to bind the zeta associated protein kinase ZAP-70. LCK then also activates ZAP-70 by phosphorylation, continuing the T cell signaling cascade. . While it is generally accepted that LCK is activated when CD4 or CD8 co-receptors are cross-linked with the TCR and MHC complex, it is also known that some LCK associates with CD8 in the absence of MHC . It is possible that LCK activation is a function of the surrounding membrane environment rather than the clustering of co-receptors with T cell receptor and MHC .
Simmons et al. Virology Journal 2006 3:8 doi:10.1186/1743-422X-3-8