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Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland
Correspondence: Susan K. Pierce, NIAID/NIH/Twinbrook II, 12441 Parklawn Drive, Room 200B, MSC 8180, Rockville, MD 20852. E-mail: spierce{at}nih.gov
The multichain immune recognition receptors (MIRRs), including the T cell and B cell antigen receptors and the high affinity receptor for IgE, play an important role in immune cell signaling. The MIRRs have no inherent kinase activity, but rather associate with members of the Src-family kinases to initiate signaling. Although a great deal is understood about the biochemical cascades triggered by MIRRs, the mechanism by which signaling is initiated was not known. The evidence now indicates that the Src-family kinases are concentrated in cholesterol- and sphingolipid-rich membrane microdomains, termed lipid rafts, that exclude the MIRRs. Upon ligand-induced crosslinking the MIRRs translocate into rafts where they are phosphorylated. The MIRRs subsequently form highly ordered, polarized structures termed immunological synapses that provide for prolonged signaling. An understanding of the biochemical composition of rafts and synapses and the mechanisms by which these form should lend insight into the regulation of immune cell activation.
Key Words: multichain immune recognition receptors • Src family kinases • tyrosine phosphorylation • immune cell activation
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