Welcome to HistoCheck - an HLA Sequence Interpreter


Introduction

Histocheck

The transplantation of hematopoietic stem cells is a potentially curative therapy for a variety of hematologic and non-hematologic diseases. HLA matching of donor and recipient is essential in order to reduce the risk of severe acute graft-versus-host disease (GVHD). Despite a continuously growing number of potential stem cell donors and cord blood units it may be impossible to find an HLA-compatible donor for carriers of rare antigens or unusual haplotypes. Furthermore, the advance of HLA typing at the allelic level will probably reveal far more subtype mismatches presently not detected.

When there is no genotypically identical sibling and there are several alternative potential donors that all have a mismatch at an HLA class I or II locus, the allogenicity of mismatches may be estimated using the Sequence Similarity Matching concept described by our working group. In this concept the amino acid differences between HLA alleles are evaluated and rated with regard to position within the molecule (peptide binding, contact with the T-cell receptor) and with regard to functional similarity of amino acids within proteins. This procedure led to a dissimilarity score (allogenicity index) whereby high values represent high dissimilarity. When there are several mismatched donors, dissimilarity scores may be calculated for any of them, and the donor with the least may be preferred.


Shared T-Cell Epitope Algorithms for HLA-DPB1

The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. Previous findings identified HLA-DPB1 alleles as targets of cytoxic T cells mediating in vivo rejection of an HSC allograft. These HLA-DPB1 alleles encode T-Cell epitopes shared by a subset of HLA-DPB1 alleles that determine non-permissive mismatches for HSC transplantation.

Retrospective evaluation of transplantations showed that the presence of non-permissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease and transplantation-related mortality but not relapse as compared with the permissive group.

Based on these findings, an algorithm for prediction of non-permissive HLA-DPB1 mismatches was developed.

Algorithm >>>