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. 2014 Apr 24;54(2):255–262. doi: 10.1016/j.molcel.2014.04.001

Figure 1.

Figure 1

The Immunological Synapse, TCR Microclusters, and TCR-Enriched Microvesicles

(A) Immunological synapse formation: when the T cell encounters the APC (antigen-presenting B cell) with appropriate MHC-peptide complexes, an immunological synapse forms with coarse segregation of TCR and bound peptide-MHC complex (pMHC) into the center (green) and a ring of LFA-1 (lymphocyte function-associated antigen 1) and ICAM-1 (intercellular adhesion molecule 1, a.k.a. CD54) (red). Microvesicles containing TCR-MHC-peptide interactions are generated from signaling microclusters, internalized by B cells, and induce signaling. The microvesicles are enriched in TCR, but their exact contents remain to be elucidated.

(B) Schematic of a TCR microcluster: this is the site in which signaling is initiated. Following phosphorylation on tyrosine residues in the cytoplasmic domains of the TCR complex by Src family kinase Lck, the zeta-associated kinase of 70 kDa (ZAP-70) tyrosine kinase is recruited and assembles the TCR signalosome with substrates including Linker of Activate T cells (LAT) (Weiss and Littman, 1994). The TCR signalosome include ubiquitin ligases c-Cbl and Cbl-b, which add multiple mono-Ub to lysine’s residues of the TCR zeta chain (Naramura et al., 2002; Cormont et al., 2003). These are recognized by Tumor suppressor gene-101 (TSG-101) to initiate microvesicle formation once the microclusters reach a sorting domain just inside the integrin ring.

(C) TCR-enriched microvesicles: optical-electron microscopy correlation has led to discovery of TCR enriched microvesicles. The actin cytoskeleton moves the microclusters downward in the schematic, and this also serves as a timeline for TCR microcluster and microvesicle formation. A signaling microcluster is initiated, the ESCRT machinery recognizes ubiquitin added to TCR in microclusters and sorts the TCR into plasma membrane buds that are released into the synapse center, and then the APC takes up the TCR-enriched vesicle, which can trigger PLCγ in the APC even in the absence of the T cell. This represents one of several mechanisms by which cells can transfer complex packets of information (Davis, 2007).