Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: A retrospective study
ABSTRACT The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation.
- SourceAvailable from: Jill A Hollenbach
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- "In addition to standard analysis at the DPB1 allele level, analysis was performed individually for these amino acid motifs, as well as for the four serological epitopes. An alternative epitope, recognized by T cells, was defined in Zino et al. (2004) (2007) and Fleischhauer et al. (2012) on the basis of alloreactive T cell cross-reactivity patterns and is therefore referred to as T cell epitope (TCE). The TCE has so far not been mapped to defined structural amino acid residues, but was surmised to impact T cell alloreactivity via variable peptide presentation and shown to determine clinically nonpermissive mismatches for DPB1 in unrelated HSCT (Zino et al. 2004, 2007). "
ABSTRACT: Here, we present results for DPA1 and DPB1 four-digit allele-level typing in a large (n = 5,944) sample of unrelated European American stem cell donors previously characterized for other class I and class II loci. Examination of genetic data for both chains of the DP heterodimer in the largest cohort to date, at the amino acid epitope, allele, genotype, and haplotype level, allows new insights into the functional units of selection and association for the DP heterodimer. The data in this study suggest that for the DPA1-DPB1 heterodimer, the unit of selection is the combined amino acid epitope contributed by both the DPA1 and DPB1 genes, rather than the allele, and that patterns of LD are driven primarily by dimer stability and conformation of the P1 pocket. This may help explain the differential pattern of allele frequency distribution observed for this locus relative to the other class II loci. These findings further support the notion that allele-level associations in disease and transplantation may not be the most important unit of analysis, and that they should be considered instead in the molecular context. Electronic supplementary material The online version of this article (doi:10.1007/s00251-012-0615-3) contains supplementary material, which is available to authorized users.Immunogenetics 04/2012; 64(8):559-69. DOI:10.1007/s00251-012-0615-3 · 2.49 Impact Factor
Article: The IMGT/HLA database[Show abstract] [Hide abstract]
ABSTRACT: It is 10 years since the IMGT/HLA database was released, providing the HLA community with a searchable repository of highly curated HLA sequences. The HLA complex is located within the 6p21.3 region of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and are highly polymorphic. The naming of these HLA genes and alleles, and their quality control is the responsibility of the WHO Nomenclature Committee for Factors of the HLA System. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute, we are able to provide public access to this data through the website http://www.ebi.ac.uk/imgt/hla/. The first release contained 964 sequences, the most recent release 3300 sequences, with around 450 new sequences been added each year. The tools provided on the website have been updated to allow more complex alignments, which include genomic sequence data, as well as the development of tools for probe and primer design and the inclusion of data from the HLA Dictionary. Regular updates to the website ensure that new and confirmatory sequences are dispersed to the HLA community, and the wider research and clinical communities.Nucleic Acids Research 11/2008; 37(Database issue):D1013-7. DOI:10.1093/nar/gkn662 · 9.11 Impact Factor
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ABSTRACT: Nucleotide sequence of HLA-DRB1*12:27 allele was different from that of HLA-DRB1*12:02:01 by three-nucleotide substitution at position 165A>C, 171G>C, and 175C>T.Tissue Antigens 07/2011; 78(6):465-6. DOI:10.1111/j.1399-0039.2011.01739.x · 2.35 Impact Factor