MHC signaling and costimulation

DC - T cell adhesion 

CD4 and CD8 molecules aid stabilization of MHC/TCR interactions. Very strong adhesion comes from ICAM-1 (DC) to LFA-1 (TC) interactions.

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Signal 1Once cell adhesion has been achieved, antigen presentation can begin. The antigen/MHC binding to the TCR provides the T cell with its first signal for activation - Signal 1.Signal 1 is not initiated however, until this process occurs at many TCRs, this is done by 'serial triggering'. MHC/TCR interactions are very weak and have a high on/off rate, meaning one MHC complex man serially trigger hundreds of TCR molecules. This increases the efficiency of antigen presentation, especially for rare MHC/peptide complexes. 100-1000s of TCR need to be triggered to activate Signal 1. Signal 2along with TCRs, and CD8/4 molecules, the T cell has CD28 molecules that will bind to CD80 on the DC, however CD80 is only expressed in the presence of a pathogen.When both Signal 1 and Signal 2 are achieved, T cell activation and proliferation is achieved. 

Signal 1 and 2

SMAC

The arrangement of immunostimulatory molecules are not evenly distributed on the cell membrane. It is divided into 3 areas of concentration, known as the SMAC - Supra-Molecular ActivationCluster.Central - TCR and costimulatory molecules e.g. CD80Peripheral - Adhesion molecules Distal - Large molecules - not covered 

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Why is costimulation necessary 

Only DCs activated by pathogen - danger signals - present CD80, therefore DCs presenting self antigen do not activate T cells. T cells that receive signal one alone are identified as responding to self antigen, they will not receive signal 2 as DCs do not present CD80 and they will undergo anergy/apoptosis - T cells become redundant. This is tolerance. In addition to this, DCs that do receive danger signals form PRR-PAMPS (TLRs) will up regulate MHC for desires immunostimulatory effects, also presenting CD80.