Structure and function of the human MHC class Ib molecules HLA‐E, HLA‐F and HLA‐G
O'Callaghan CA., Bell JI.
Summary: The major histocompatibility (MHC) class Ib molecules HLA‐E, HIA‐F and HLA‐G are relatively non‐polymorphic compared to class la molecules. Both HLA‐E and HLA‐G bind peptides and are involved in natural killer (NK)‐cell recognition, but the role of HLA‐F is unclear. HLA‐E binds specifically to the conserved leader sequence peptides from the class la MHC molecules and interacts on the cell surface with the CD94/NKG2 class of NK‐cell receptors. The framework structure of HLA‐E is similar to that of the MHC class la molecules, but the peptide‐binding groove is highly adapted for the specific binding of the leader sequence peptides. This is different from class la molecules, which have highly promiscuous peptide‐binding grooves. The HLA‐E groove makes full use of all the available pockets and imposes specificity along the entire length of the peptide. HLA‐G binds nonamer peptides with leucine or isoleucine at position 2, proline at position 3 and leucine at position 9. Expression of HLA‐G inhibits NK cells expressing the CD94/NKG2 class of receptors, though an interaction with these receptors has not been directly demonstrated.