Figure 24–46 early signaling events in a b cell activated by the binding of specific foreign antigen to its bCRs. If the antigen is on the surface of a pathogen or is a soluble macromolecule with two or more identical antigenic determinants (as shown), it cross-links adjacent Bcrs, causing them and their associated invariant chains to cluster, as shown. A Src-like cytoplasmic tyrosine kinase (which can be Fyn or Lyn) is associated with the cytosolic tail of Igβ; it joins the cluster and phosphorylates both the Igα and Igβ invariant chains (for simplicity, only the phosphorylation on Igβ is shown). A transmembrane protein tyrosine phosphatase called CD45 is also required to remove inactivating phosphates from these Src-like kinases (not shown). The resulting phosphotyrosines on Igα and Igβ serve as docking sites for another Src-like tyrosine kinase called Syk, which becomes phosphorylated and thereby activated to relay the signal downstream.
The pathway from Tcrs is similar (including a requirement for cD45), except that the first Src-like kinase is Lck, which is associated with a cD4 or cD8 co-receptor and phosphorylates tyrosines on all the cD3 polypeptide chains shown in Figure 24–45B; the second Src-like kinase is ZAP70, which is homologous to the Syk kinase in B cells (Movie 24.14).
Many cell-Surface proteins Belong to the Ig Superfamily
Most of the proteins that mediate antigen recognition and cell–cell recognition in the immune system contain one or more Ig or Ig-like domains, suggesting that the proteins have a common evolutionary history. Included in this very large Ig superfamily are antibodies, TCRs, MHC proteins, the CD4, CD8, and CD28 co-receptors, the B7 co-stimulatory proteins, and most of the invariant polypeptide chains associated with TCRs and BCRs, as well as the various Fc receptors on lymphocytes and other leukocytes. Many of these proteins are dimers or higher oligomers, in which Ig or Ig-like domains of one chain interact with those in another (Figure 24–48).