7p49

Publication Abstract from PubMed

MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8(+) T cells. To understand these affinity differences, human MHC-E (HLA-E)-VL9 versus pathogen-derived peptide structures are compared. Small-angle X-ray scatter (SAXS) measures biophysical parameters in solution, allowing comparison with crystal structures. For HLA-E-VL9, there is concordance between SAXS and crystal parameters. In contrast, HLA-E-bound pathogen-derived peptides produce larger SAXS dimensions that reduce to their crystallographic dimensions only when excess peptide is supplied. Further crystallographic analysis demonstrates three amino acids, exclusive to MHC-E, that not only position VL9 close to the alpha2 helix, but also allow non-VL9 peptide binding with re-configuration of a key TCR-interacting alpha2 region. Thus, non-VL9-bound peptides introduce an alternative peptide-binding motif and surface recognition landscape, providing a likely basis for VL9- and non-VL9-HLA-E immune discrimination.

Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes.,Walters LC, Rozbesky D, Harlos K, Quastel M, Sun H, Springer S, Rambo RP, Mohammed F, Jones EY, McMichael AJ, Gillespie GM Cell Rep. 2022 Jun 14;39(11):110959. doi: 10.1016/j.celrep.2022.110959. PMID:35705051^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.