The pMHC class I complex
Peptide-major histocompatibility complex class I (pMHCI) is expressed on the surface of almost all nucleated cells in the body and allows CD8+ T-cells (CTLs) to scan for abnormalities and infections.
What is the role of pMHCI in the immune system?
CTLs kill virally infected cells and tumours. In order to carry out this important function, CTLs recognise short fragments of foreign proteins presented by MHCI via an interaction with the TCR. This process is essential for immunity to many intracellular pathogens as CTLs are the only tools by which the immune system can scan the cellular proteome for anomalies. 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.
Why is it important to study pMHCI?
Small peptide fragments, representing the entire cellular proteome, 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 anomalies. MHCI present short peptides (generally 8-12 amino acid residues long) which are anchored into the MHC binding groove. 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 and respond.