Fig. 10.

Left panel: model of activation of T-cells by adhesion domains formed during the initial phase of T-cell–APC encounters (before the formation of large central SMACs). The kinase ZAP-70 is activated by binding to the phosphorylated tyrosine groups of the cytoplasmic chain of the co-receptor CD3. The non-adhesive state occurs due to the abolishment of ZAP activation by CD45-mediated ongoing de-phosphorylation of CD3. The adhesive state leading to the formation of immune synapse (IS) is promoted by the clustering of bound TCR–MHC–AG pairs, which results in the expulsion of the inhibitor CD45 from the reaction center by steric forces. Right panel: demonstration of the CD45 self-inhibition model by Choudhuri and collaborators.⁶⁴ By reducing the length of the extracellular domain, CD45 can diffuse into the tight adhesion domain and prevent the activation of ZAP by continuous removal of phosphate groups at the CD3-coreceptor. The same effect was observed by prolongation of the extracellular domains of the MHC–receptor. In summary, the phosphatase CD45 plays a twofold role: it inhibits the CD3-phosphorylation, and, together with other glycoproteins of the glycocalyx (e.g. CD43), acts as a buffer molecule counteracting adhesion.