T cells

The structures of pMHC complexes have provided answers to key questions concerning their overall conformation and antigen presentation. From such studies it has become clear that certain MHC types are restricted in terms of the peptide sequences they can successfully present. This is mostly due to the identification of important peptide anchor residues that form specific interactions with the MHC binding groove. In the case of pMHC I, for example, the interactions of peptide position 2 with the MHC B-pocket, and the terminal peptide residue with MHC F-pocket are of particular importance. Therefore, only certain residues at these positions will support stable antigen presentation.

Cytotoxic T-cells (CTLs) kill virally infected cells and tumours. In order to carry out this important function, CTLs recognise short fragments of foriegn proteins presented by pMHCI. This process is essential for immune responses against harmful pathogens. pMHCI comprise of an alpha -domain and beta 2m. beta 2m is comprised mainly of beta -sheets, and it associates loosely with the MHC complex. Peptides are presented in a groove between by the MHC alpha 1 and alpha 2-domains formed from two long alpha -helices and a beta -sheet domain, which provides the floor of the binding groove. The alpha 3-domain, which is comprised mainly of beta sheets, is linked to the cell surface via a transmembrane-domain.

A - Crystal structure of pMHCI. B - The MHC binding pockets (A-F) which form specific interactions with conserved peptide anchor residues. C - The peptide conformation in MHCI molecules is characterised by a prominent central bulge which forms the main platform for the antigen specific TCR interaction.