Cutting antigenic peptides down to size

Abstract

A critical step in antigen presentation is the degradative processing of peptides by aminopeptidases in the endoplasmic reticulum. It is unclear whether these enzymes act only on free peptides or on those bound to their major histocompatibility complex (MHC)-I-presenting molecules. A recent study examined the structure and biophysics of N-terminally extended peptides in complex with MHC-I, revealing the conformational adjustment of MHC to permit both binding of the peptide core and exposure of the peptide N terminus. These data suggest a mechanism by which aminopeptidase access is determined and offer an explanation for how longer peptides may be displayed at the cell surface.

Figure 1.

Comparison of the structure of pMHC-I complex containing N-terminally extended peptide with canonical octamer-peptide/MHC-I complex reveals reorientation of p1 amine of peptide and side chain of MHC-I residue Arg-62. A ribbon diagram of the previously determined structure of HLA-B*08:01 complexed with an octamer peptide (GGKKKYKL) (PDB entry 1AGD) (A and C) is compared with that of HLA-B*08:01E76C complexed with a 10-mer (RAAAKKKYCL) (PDB entry 6P2S) (B and D) as described in detail by Li et al. (4). Attention is focused on the position of the side chain of Arg-62 of the α1 helix and the orientation of p1 nitrogen (in blue). In C and D, a surface representation of the residues lining the A pocket is shown.