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Journal of Immunology Research
Volume 2014 (2014), Article ID 159479, 12 pages
Review Article

Predicting Alloreactivity in Transplantation

Laboratory for Translational Immunology, UMC Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands

Received 14 February 2014; Accepted 13 April 2014; Published 28 April 2014

Academic Editor: Trevor Huyton

Copyright © 2014 Kirsten Geneugelijk et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Human leukocyte Antigen (HLA) mismatching leads to severe complications after solid-organ transplantation and hematopoietic stem-cell transplantation. The alloreactive responses underlying the posttransplantation complications include both direct recognition of allogeneic HLA by HLA-specific alloantibodies and T cells and indirect T-cell recognition. However, the immunogenicity of HLA mismatches is highly variable; some HLA mismatches lead to severe clinical B-cell- and T-cell-mediated alloreactivity, whereas others are well tolerated. Definition of the permissibility of HLA mismatches prior to transplantation allows selection of donor-recipient combinations that will have a reduced chance to develop deleterious host-versus-graft responses after solid-organ transplantation and graft-versus-host responses after hematopoietic stem-cell transplantation. Therefore, several methods have been developed to predict permissible HLA-mismatch combinations. In this review we aim to give a comprehensive overview about the current knowledge regarding HLA-directed alloreactivity and several developed in vitro and in silico tools that aim to predict direct and indirect alloreactivity.