Biochemical features of HLA-B27 and antigen processing

Abstract

The strong association of the human MHC class I alleleHLA-B27 with the development of th e chronic inflammator y disease ankylosingspondylitis (AS) is clear and has been known for over three decades. Despite thi s. it is far from clear how HLA-R27 is directly involved in AS. In recent years considerable progress has been made in defining the assembly pathway and the protein components involved in successfully folding MHC class I molecules in the environment ofthe endoplasmic reticulum. This process involves a number ofcritical interactions. which may influence how HLA-B27 molecules fold and what peptides become loaded. The impact of the unpaired Cys-67 residue in the peptide-binding groove upon the behaviour of both correctly fold ed and misfolded HLA-B27 molecules , especially its ability to allow the formation of B27 heavy-chain oligomers or dimers, which may form novel targets for immune receptors. or be an indicator ofintracellular stress, has also been the focus ofmuch research. In this chapter we aim to review recent data to determine whether any biochemical features of HLA-B27 can supply clues as to its enigmatic role in AS and will also comment on future potential directions of biochemical research into HLA-B27. © 2009 Landes Bioscience and Springer Science+Business Media.