An Approach to Predicting Hematopoietic Stem Cell Transplantation Outcome Using HLA-Mismatch Information Mapped on Protein Structure Data

作者：Dudkiewicz Malgorzata^*; Malanowski Piotr; Czerwinski Jaroslaw; Pawlowski Krzysztof

来源：Biology of Blood and Marrow Transplantation, 2009, 15(9): 1014-1025.

DOI：10.1016/j.bbmt.2009.05.011

• Hematopoietic stem cell transplantation
• HLA mismatch
• Donor-recipient matching
• HLAp-T cell receptor complex
• Protein structure analysis
• Conformational search

In hematopoietic stem cell transplantation (HSCT), the outcome is predicted using HLA-matching procedures, which are very time-consuming. There exists substantial evidence of the importance of early donor acceptance in HSCT outcome. In cases when the donor cannot be perfectly matched, it often is unclear which mismatch is less harmful and thus has a greater likelihood of acceptance. We modeled and analyzed interactions between the protein products of different HLA alleles of the transplant recipient and natural killer and T lymphocyte cell receptors of the donor's immune system. Reactions between these 2 systems often lead to graft-versus-host disease (GVHD). Sequence polymorphisms that define HLA I and 11 alleles predict not only GVHD, but also host-versus-graft and graft-versus-leukemia effects, all of which influence the overall transplantation outcome. Although complete high-resolution HLA matching of the donor-recipient pair seems to be associated with optimal post-HSCT survival, recent reports suggest that not every HLA disparity is functionally relevant. We performed interaction energy calculations for selected pairs of donor-recipient HILA alleles. Based on the results, we conclude that the energy of contact between the T lymphocyte cell receptor (TCR) and HLA residues can help predict the fut

• 出版日期2009-9