Spatial coordination of CD8 and TCR molecules controls antigen recognition by CD8+ T-cells

The interactions between the TCR and peptides bound to class I MHC encoded molecules (pMHC) and a mechanism for CD8 cooperation in this process are reviewed. Observation of two TCR/CD8 populations with different lateral diffusion rate constants as well as two distinct association phases of class I MHC tetramers ((pMHC)4) with T-cells suggest that the most efficient pMHC–T-cell association route corresponds to a fast tetramer binding to a colocalized CD8/TCR population, which apparently resides within membrane rafts. Thus, ligand–cell association starts by pMHC binding to the CD8. This rather fast step promotes pMHC association with CD8–proximal TCRs and thereby enhances the overall association process. The model suggests that this raft-associated CD8–TCR subpopulation is responsible for evoking T-cell activation.