Diverse locations of amino acids in HLA-DRβ chains involved in polymorphic antibody binding epitopes on DR(α,β1^*0101), DR(α,β1^*1101), and DR(α,β3^*0202) molecules

In a previous study, we used transfectants expressing hybrid HLA-DR(β1^*0403)/DR(β1^*0701) chains to map sequences involved in polymorphic antibody binding epitopes on DR(α,β1^*0403) or DR(α,β1^*0701) molecules. Amino acids 1-40 of the β₁ domain were found to make the major contributions to most of the antibody binding epitopes studied. To begin to localize sequences that contribute to polymorphic antibody epitopes on DR(α,β1^*0101), DR(α,β1^*1101) and DR(α,β3^*0202) molecules, we used indirect immunofluorescence and flow cytometry to assess the binding of mAb to transfectants expressing hybrid DR(β1^*0101)/DR(β1^*1101) or DR(β1^*1101)/DR(β3^*0202) chains that divide the DRβ chain into three segments: amino acids 1-40, 41-97, and the β₂ domain. The results indicate that amino acids 41-97 of the β₁ domain on DR(β1^*0101), DR(β1^*1101), or DR(β3^*0202) are critical in most of the epitopes, including those recognized by human antibodies MP4 and MP12, and mouse mAb GS88.2, I-LR1, 21r5, and 7.3.19.1, whereas amino acids 1-40 of DR(β1^*1101) are critical in the epitope recognized by the MCS-7 mAb, and both segments 1-40 and 41-97 of DR(β1^*1101) are important in the epitopes recognized by the I-LR2 and UL-52 mAbs. Based on these data and comparison of DRβ allelic protein sequences, the residues that may play critical roles in these antibody binding epitopes are predicted.