Antigen (Ag) and Superantigen (SAG)
More to come soon
TCR-CD3-CD4 complex
Ternary complex between the CD4, MHCII and CD4. (a) Schematic of a docked pMHC with the TCR-CD3 multireceptor complex and CD4. (b) Ribbon formatted crystal structure of the MS2-3C8 TCR, MBP-DR4 and CD4 complex and the CD3 gamma-delta and gamma-epsilon subunits (PDB 3T0E).
Ternary complex between the CD4, MHCII and CD4. (a) Schematic of a docked pMHC with the TCR-CD3 multireceptor complex and CD4. (b) Ribbon formatted crystal structure of the MS2-3C8 TCR, MBP-DR4 and CD4 complex and the CD3 gamma-delta and gamma-epsilon subunits (PDB 3T0E).
TCR signaling pathway
(1) The white boxes represent the major members of the proximal signaling complex: Lck, LAT, ZAP-70 and PLC-g1 initiate the signaling cascade and the hydrolysis of PIP2. (2) Binding of IP3 to its receptor triggers a Ca2+ flux from the ER and cell membranes and activates NF-AT. DAG recruits PKC-q and RasGRP to the plasma membrane, which prompts NF-kB’s activation (3) and to the positive feedback loop responsible for Ras activation (4), respectively.
(1) The white boxes represent the major members of the proximal signaling complex: Lck, LAT, ZAP-70 and PLC-g1 initiate the signaling cascade and the hydrolysis of PIP2. (2) Binding of IP3 to its receptor triggers a Ca2+ flux from the ER and cell membranes and activates NF-AT. DAG recruits PKC-q and RasGRP to the plasma membrane, which prompts NF-kB’s activation (3) and to the positive feedback loop responsible for Ras activation (4), respectively.
T cell signaling complexes
Cartoons illustrating the major docking topologies between MHCII and TCR, whether or not mediated by SAG. From left to right are pictured the canonical, SEB-, SEA-, MAM- and vSAG-mediated T cell signaling complexes.
Cartoons illustrating the major docking topologies between MHCII and TCR, whether or not mediated by SAG. From left to right are pictured the canonical, SEB-, SEA-, MAM- and vSAG-mediated T cell signaling complexes.
Transmission and infection cycle of MMTV
The exogenous MMTV transmission is milk-borne; virions contained in ingested milk first infect DCs (1) then spread to B and T cells in the Peyer’s patches and ultimately, with the help of its vSAG (2), to other lymph nodes and lymphoid organs. A rapid T cell proliferation follows, providing help to B cells and recruiting additional lymphocytes (3), leading to a pool of infected cells. These cells gain access to mammary glands (4), a mucosal-associated lymphoid tissue (MALT), in which the virus replicates (5) and is later shed via the milk (6). Because of the vSAG, a slow and almost complete deletion of cognate Vb T cells follows the infection (7). As a result of the virus’ multiple integration in lymphocytes (8) and mammary gland epithelial cells, tumorigenesis may arise to varying degrees (9). Germline transmitted, endogenous MMTVs cause thymic negative selection of vSAG-cognate T cells (I) leading to deletion (II). Most of endogenous viruses are unable to produce infectious particles.
