EFFECT OF POLYMORPHISM OF THE HLA-DPA1 CHAIN ON PRESENTATION OF ANTIGENIC PEPTIDES

Human T-cell clones that recognize a peptide from mycobacterial heat s hock protein 60 in the context of HLA-DP were found to be sensitive to changes in the DPA1 chain of the restricting element, optimal respons es being seen with the combination HLA-DPA10201 and HLA-DPB*0301. HLA -DP dimers containing HLA-DPA101 were only able to present antigenic peptides co T-cell clones when peptides were present throughout the pe riod of coculture of T cells with antigen presenting cells. In contras t the optimal HLA-DP dimer could also stimulate T-cell clones maximall y when incubated with peptides for 1 h and then thoroughly washed. Thi s suggests that the DPA1 polymorphism influenced the strength of bindi ng of antigenic peptides to the HLA-DP dimer. Modeling studies identif ied amino acid 31 of DPA1 as the polymorphic residue most likely to ac count for this effect. This is the first demonstration chat the relati vely limited polymorphism displayed by DPA1 has functional consequence s. (C) American Society for Histocompatibility and Immunogenetics, 199 7.