title: Effect of polymorphism of the HLA-DPA1 chain on presentation of antigenic peptides.
abstract: Human T-cell clones that recognize a peptide from mycobacterial heat shock protein 60 in the context of HLA-DP were found to be sensitive to changes in the DPA1 chain of the restricting element, optimal responses being seen with the combination HLA-DPA1*0201 and HLA-DPB*0301. HLA-DP dimers containing HLA-DPA1*01 were only able to present antigenic peptides to T-cell clones when peptides were present throughout the period of coculture of T cells with antigen presenting cells. In contrast the optimal HLA-DP dimer could also stimulate T-cell clones maximally when incubated with peptides for 1 h and then thoroughly washed. This suggests that the DPA1 polymorphism influenced the strength of binding of antigenic peptides to the HLA-DP dimer. Modeling studies identified amino acid 31 of DPA1 as the polymorphic residue most likely to account for this effect. This is the first demonstration that the relatively limited polymorphism displayed by DPA1 has functional consequences.
authors.affiliation: Department of Medicine, University of Cambridge, United Kingdom.
authors.forename: J S
authors.initials: JS
authors.lastname: Gaston
authors.forename: J C
authors.initials: JC
authors.lastname: Goodall
authors.forename: J L
authors.initials: JL
authors.lastname: Young
authors.forename: S P
authors.initials: SP
authors.lastname: Young
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics*; D018834:Chaperonin 60 / Q000276:immunology; D002999:Clone Cells; D006682:HLA-DP Antigens / Q000737:chemistry / Q000235:genetics*; D059867:HLA-DP alpha-Chains; D006801:Humans; D008213:Lymphocyte Activation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018834:Chaperonin 60; D006682:HLA-DP Antigens; D059867:HLA-DP alpha-Chains; C071172:HLA-DPA1 antigen; D010455:Peptides