Peptide-major histocompatibility complex class II (pMHCII) is expressed on the surface of specialised cells in the body and allow CD4+ T-cells (Th cells) to scan for abnormalities and infections.
Th cells carry out a number of functions, including orchestrating immune responses against bacteria and parasites. In order to carry out this important function, Th cells recognise short fragments of foreign proteins presented by pMHCII via an interaction with the TCR. This process is essential for immune responses against harmful pathogens as it enables Th cells to check for anomalies inside self cells by scanning their surface. CD4 is also involved in Th cell co-activation by binding to a distinct invariant region of the pMHCII molecule. This tripartite (TCR/pMHC/CD4) 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 pMHCII α1 and β1-domains, which is topologically similar to pMHCI. MHC II present peptides 10-25 residues in length are more buried within the MHC surface compared to MHCI. Thus, MHCII presented peptides generally have a less prominent central bulge compared to pMHCI which is theoretically less favourable surface for TCR docking. This 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.