A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 Allotypes. (4th December 2014)

• Record Type: Journal Article
• Authors: Badrinath, Soumya; Kunze-Schumacher, Heike; Blasczyk, Rainer; Huyton, Trevor; Bade-Doeding, Christina
• Other Names: Clerici Mario Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2014(2014)
• Publication Date: 2014-12-04
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2014/298145
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A * 24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities. HLA-A * 24:06 156Trp and HLA-A * 24:13 156Leu showed high levels of cell surface expression while HLA-A * 24:02 156Gln was expressed at low levels in tapasin deficient cells. Peptides presented by these allelic variants showed distinct differences in features and repertoire. Immunoprecipitation experiments demonstrated all the HLA-A * 24/156 variants to associate at similar levels with tapasin when present. Structurally, HLA-A * 24:02 contains the residue triad Met97/His114/Gln156 and a Trp156 or Leu156 polymorphism provides tapasin independence by stabilizing these triad residues, thus generating an energetically stable and a more peptide receptive environment. Micropolymorphisms at position 156 can influence the generic peptide loading pathway for HLA-A * 24 by altering their tapasin dependence for peptide selection. The trade-off for this tapasin independence could be the presentation of unusual ligands by these alleles, imposing significant risk following hematopoietic stem cell transplantation (HSCT).