- The physical interaction between T-cell Receptor (TCR) and its specific peptide in complex with MHC is actually quite weak and requires structural stabilization. Stabilization of the TCR:peptide:MHC complex is provided by T-cell Coreceptors which are expressed as membrane proteins on T-cells.
- Two subtypes of T-cell Coreceptor exist, CD4 and CD8, which display strong specificity for particular MHC classes. The CD4 coreceptor can only stabilize TCR:MHC II complexes while the CD8 coreceptor can only stabilize the TCR:MHC I complex. Consequently, although there are no important subtypes of TCR itself, differential expression of CD4 and CD8 on different T-cell populations allows functional subpopulations of T-cells to exist. As a result, CD4+ T-cells which express CD4 can only interact with MHC II while CD8+ T-cells which express CD8 can only interact with MHC I.