Epitope mapping of the complex HLA-Alloantibody

Chronic organ transplant failure is mostly mediated by the interaction between proteins expressed on the donor organ, Human Leukocyte Antigen (HLA), and Alloantibodies generated by the recipient. HLA proteins can be divided into two groups: Class I are expressed by nucleated cells and Class II by antigen-presenting cells. Immunological risk assessments are performed using binding assays on both HLA classes to check the histocompatibility between donor and recipient, however, these tests are difficult to interpret since there is a lack of structural information on this kind of interactions. We previously determined four models, two HLA Class I – Alloantibodies complexes at 3.5 Å and 2.9 Å resolution and two Class II – Alloantibodies at 2.7 Å and 3 Å, allowing us to identify four new immunogenic epitopes and to map the important interactions. To provide even more molecular insights, new clinically relevant Class II – Alloantibody complexes are now the targets of our structural studies.