Welcome to HistoCheck - an HLA Sequence Interpreter


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Histocheck

HistoCheck evaluates amino acid differences between pairs of HLA alleles, which are relevant for stem cell transplantation (including alleles of different molecular groups). Currently, HLA class I (HLA-A,B,C) and class II (DRB1, DQB1, DPB1) are available for this comparison. HistoCheck indicates the positions of exchanges, and checks whether these positions can be assigned to the peptide binding site or to the region likely to have contact with the T-cell receptor.

Newly described HLA sequences are regularly integrated into the database according to the nomenclature for factors of the HLA system updates.

Due to the strong structural homology between HLA class I molecules, the assignment of amino acid residues to functional regions also of HLA-B and C is based on HLA-A2 (Madden et al.). The assignment of positions is given in Table 1.

The same constellation applies to HLA class II, where the the assignment of the amino acid residues of the DQB1 encoded DQ ß chains refers to the the ß chain of the HLA-DR1 molecule [Brown et al; Hennecke et al.; Stern et al.]. The assignment of positions is given in Table 2.

Functional dissimilarity of exchanged residues is shown according to the score proposed by Risler (See Table 3). These data are used to calculate an overall dissimilarity score (See Algorithm). A low score indicates a low probable allogenicity between HLA variants.

In addition to these calculations HistoCheck visualizes the HLA amino acid differences between donor and recipient in a graph which is shown by the integrated RasMol software (Sayle et al.). This image is based upon either the PDB file for HLA-A*0201 and as reported by Madden, et al. (See PDB File Ref. #1) or the PDB file for DRB1*0101 as reported by Stern et al. (See PDB File Ref. #2). After the query, the RSM files containing the highlighted differences can be downloaded for further studies.


Shared T-Cell Epitope Algorithms for HLA-DPB1

HistoCheck assigns HLA-DPB1 alleles to one of the TCE3 and TCE4 groups and calculates their permissiveness and non-permissiveness for mismatching in Host versus Graft and Graft versus Host direction based on the TCE3 and TCE4 algorithm. The database used for grouping is either evidence-based (1, 2) or has been calculated from the HLA sequence database and is updated on a regular basis when new sequences become available. This sequence-based grouping relies on sequence features observed in the few alleles for which experimental evidence is available and needs experimental or clinical confirmation.

A Shared T-Cell Epitope Algorithm is currently available only for HLA-DPB1.

Newly described HLA sequences are regularly integrated into the database according to the nomenclature for factors of the HLA system updates.
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