Immunogenic HLA class I epitopes identified by humoral response to pregnancies

The main objective of this study was to understand the humoral immunity against HLA so that this knowledge can be applied clinically. We investigated the various factors resulting in antibody production by 128 mothers against the child's inherited paternal alleles. Among 128 mother-child pairs, 39 different mismatch antigens were observed. Of these, 19 resulted in antibody production against the specific mismatched antigen. The 20 mismatched antigens that did not result in a humoral immune reaction were excluded from this study. We performed epitope analysis by testing 45 allo-antisera from mothers. We compared the amino acids that define these epitopes in the mother's HLA with those in the immunogen's HLA. The positions of the mismatched amino acids between them were determined to be the immunogenic amino acid positions of mismatched HLA. We found that the immunogenic epitopes were located mainly on the alpha 1 helix. Mothers who have different immunogens were shown to have different class II alleles. Epitope analysis of this study indicated the possibility that immunogenic amino acid positions exist for each of the different mismatching alleles. Mismatching at these immunogenic positions did not always result in the antibody production, and it is thought that the differences are due to the efficiency of class II alleles in presenting the mismatched alleles.