The Mechanism of ß2m Molecule-Induced Changes in the Peptide Presentation Profile in a Bony Fish.

ABSTRACT

Contemporary antigen presentation knowledge is based on the existence of a single ß2m locus, and a classical MHC class I forms a complex with a peptide (i.e., pMHC-I) to trigger CTL immunity. However, two ß2m loci have been found in diploid bony fish; the function of the two ß2m molecules is unclear. Here, we determined the variant peptide profiles originating from different products of the ß2m loci binding to the same MHC-I molecule and further solved the crystal structures of the two pMHC-I molecules (i.e., pCtid-UAA-ß2m-2 and pCtid-UAA-ß2m-1-II). Of note, in pCtid-UAA-ß2m-2, a unique hydrogen bond network formed in the bottom of the peptide-binding groove (PBG) led to α2-helix drift, ultimately leading to structural changes in the PBG. The mechanism of the change in peptide presentation profiles by ß2m molecules is illustrated. The results are also of great significance for antivirus and antitumor functions in cold-blooded vertebrates and even humans.