Peptide-major histocompatibility complex class I (pMHCI) is expressed on the surface of almost all nucleated cells in the body and allow CD8+ T-cells (CTLs) to scan for abnormalities and infections.
CTLs kill virally infected cells and tumours. In order to carry out this important function, CTLs recognise short fragments of foreign proteins presented by pMHCI via an interaction with the TCR. This process is essential for immune responses against harmful pathogens as it enables CTLs to indirectly check for anomalies inside cells by scanning their surface. CD8 is also involved in CTL co-activation by binding to a distinct invariant region of the pMHCI molecule. This tripartite (TCR/pMHC/CD8) complex formation has a major role in T-cell activation.
Small peptide fragments, representing the entire cellular content, are presented in a groove formed between the MHCI α1 and α2-domains. These pMHCIs are transported to the cell surface allowing antigen specific TCRs to scan for foreign signals. MHCI present peptides 8-12 residues long which are anchored onto the surfaced of the MHC. The middle of the peptide bulges out away from the MHC surface, easily accessible for the TCR. This central bulge, and the rest of the MHC peptide binding platform, is central to T-cell immunology, because only T-cells with TCRs that can recognise this surface will have the ability to activate.