Distinct mechanisms survey the structural integrity of HLA-B*27:05 intracellularly and at the surface

• DOI: 10.1371/journal.pone.0200811
• Publication Date: 2018-08-02T13:32:46Z
• Authors: Zeynep Hein; Britta Borchert; Esam Tolba Abualrous; Sebastian Springer
• Keywords: Pathogenesis; HLA-B; Allotype

HLA-B*27:05 is associated with the development of autoimmune spondyloarthropathies, but precise causal relationship between MHC haplotype and disease pathogenesis yet to be elucidated. Studies focusing on structure cellular trafficking implicate several links onset inflammation unusual conformations molecule inside at surface antigen presenting cells. Several lines evidence emphasize emergence those unnatural protein under conditions where peptide loading onto B*27:05 impaired. To understand how factors distinguish poorly loaded molecules from optimally ones, we have investigated intracellular transport, folding, cell expression this particular B27 subtype. Our findings show that structurally unstable in absence peptide, an artificially introduced disulfide bond residues 84 139 conferred enhanced conformational stability suboptimally molecules. Empty or can escape retention arrive leading appearance increased number β2m-free heavy chains. study reveals a general mechanism found early secretory pathways murine human cells apply quality control class I molecules, it highlights allotype-specific structural features aberrant presentation might contribute etiology disease.