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DOI :10.26650/B/ET07.2022.012.14   IUP :10.26650/B/ET07.2022.012.14    Full Text (PDF)

Dpb1 T-Cell Epitope Algorithms for Selection of Allogeneic Hematopoietic Stem Cell Donor

Demet KıvançHayriye Şentürk ÇiftçiSüleyman Rüştü OğuzFatma Savran Oğuz

Human leukocyte antigen (HLA) expression levels have been thought to be genetically controlled by single nucleotide polymorphisms (SNPs) in the untranslated regions (UTRs). HLA expression variants have been associated with successful hematopoietic stem cell transplantation (HSCT). The generally accepted match rate in unrelated donor searching is at the high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci, but recent studies have shown that HLA-DPB1 mismatches between patient and donor can induce alloreactive T-cell responses, which has also been shown to be able have an effect on the development of acute graft-versus-host disease (aGvHD) and overall survival after allogeneic hematopoietic stem cell transplantation (AHSCT). The classification of HLADPB1 mismatches based on T cell epitope (TCE) groups has been shown to determine permissive and non-permissive mismatches after AHSCT. HLA-DPB1 alleles are classified under four different TCE groups, which are predicted to have a high, moderate, low, or intermediate immunogenic potential based on their T-cell cross-reactivity patterns. The distinction between permissive and non-permissive HLA-DPB1 mismatches is based on whether donor and patient alleles are from the same or different TCE groups, and the HLA-DPB1 TCE match can be estimated using a simple online tool. Recent research has led to the development of a functional epitope-based algorithm that analyzes HLA-DPB1 mismatches based on T-cell alloreactivity patterns targeting HLA-DPB1 antigens. A web-based tool for applying the algorithm to unrelated donor searches is available using the IMGT-HLA database (http://www.ebi. ac.uk/ipd/imgt/hla/dpb.html). These algorithms allow a patient and donor to load the HLA-DPB1 type into the online tool and display the predicted T-cell epitopes and the resulting mismatch effect in the direction of GvHD or Host-versus-graft (HvG) disease when selecting suitable donors for AHSCT recipients.


DOI :10.26650/B/ET07.2022.012.14   IUP :10.26650/B/ET07.2022.012.14    Full Text (PDF)

Allojeneik Hematopoietik Kök Hücre Donörü Seçiminde Dpb1 T-Hücre Epitop Algoritmaları

Demet KıvançHayriye Şentürk ÇiftçiSüleyman Rüştü OğuzFatma Savran Oğuz

İnsan Lökosit Antijeni (HLA) ekspresyon seviyelerinin, UTR bölgelerindeki (untranslated region) tek nükleotid polimorfizmleri (SNP) tarafından genetik olarak kontrol edildiği düşünülmekte olup, ekspresyon varyantları hematopoietik kök hücre nakli (HKHN) başarısı ile ilişkilendirilmiştir. Akraba dışı donör taramasında genel olarak kabul edilen uyum oranı yüksek çözünürlükte HLA-A, -B, -C, -DRB1 ve -DQB1 lokusu seviyesinde iken son zamanlarda yürütülen çalışmalar, HLA-DPB1 lokusu için hasta ve donör arasında mevcut olan uyumsuzlukların alloreaktif T-hücre yanıtlarını indükleyebileceğini ve allojeneik hematopoietik kök hücre nakli (AHKHN) sonrası akut graft versus host hastalığı (aGvHH) gelişimi ve genel sağ kalım üzerinde etkili olabileceğini göstermiştir. HLADPB1 uyumsuzluklarının T hücre epitop (TCE) gruplarına dayalı olarak sınıflandırılmasının, AHKHN’den sonra tolere edilebilecek (permissive) ve tolere edilmeyen yani riskleri artıracak (non-permissive) uyumsuzlukları belirlediği gösterilmiştir. HLA-DPB1 allelleri, T-hücre çapraz reaktivite paternleri temelinde yüksek, orta, düşük ve ara immünojenik potansiyele sahip olduğu tahmin edilen 4 farklı TCE grubu şeklinde sınıflandırılır. Permissive ve non permissive HLA-DPB1 uyumsuzluklarının ayrımı, hasta ve donör alellerinin aynı veya farklı TCE gruplarından olup olmamasına göre yapılır ve basit bir çevrimiçi araç ile HLA-DPB1 TCE eşleşmesi tahmin edilebilir. Son araştırmalar, HLA-DPB1 antijenlerini hedef alan T hücresi alloreaktivite modellerine dayalı olarak HLA-DPB1 uyumsuzluklarını analiz eden işlevsel “epitop tabanlı” bir algoritma geliştirilmesini sağlamıştır. Algoritmanın akraba dışı verici araştırılmalarında uygulanması için web tabanlı bir araç, IMGT-HLA veritabanı aracılığıyla kullanıma sunulmuştur (http://www.ebi.ac.uk/ipd/imgt/hla/dpb.html). Bu algoritmalar, bir hasta ve donörün HLADPB1 tipinin çevrimiçi araca yüklenmesi ve AHKHN alıcıları için uygun donörleri seçerken tahmin edilen T Hücre epitoplarını ve sonuçta ortaya çıkan GvHH veya Host versus graft (HvG) yönündeki uyumsuzluk etkisinin tahmini olarak görüntülenmesine izin verir.



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