HLA Moleküllerinde Peptit Ligandlarının Kompleks Stabilitesine Olan Etkisinin Araştırılması

Öz

Hücre yüzey glikoproteinleri olan Temel Doku Uygunluk Kompleks (MHC) molekülleri yabancı antijenlere bağlanır ve onları uygun immün tanınma için antijen sunucu hücrelerin yüzeyindeki T lenfosit hücrelerine sunar. İlk olarak insanlarda lökosit hücrelerinde tanımlanmış oldukları için, aynı zamanda İnsan Lökosit Antijenleri (HLA) olarak da isimlendirilirler. Son zamanlarda peptit bazlı aşıların tasarlanması üzerine odaklanan çalışmalar, peptitin sitotoksik T hücre aracılı immün cevabı uyarma yeteneği olarak tanımlanan peptit immunojenite mekanizmasının anlaşılmasına olanak sağlamaktadır. Peptit immünojenisitesinin, peptit-HLA kompleksinin stabilitesi ile ilişkili olduğu bilinmektedir. Bu çalışmada, AIFQSSMTK and QVPLRPMTYK peptitlerine bağlanan HLA-A*03:01 ve HLA-A*11:01 alellerinin stabilitesinin temel moleküler mekanizmalarını ortaya çıkarmak için moleküler dinamik simülasyonları gerçekleştirilmiştir ve ENCOM sunucusu kullanılarak peptit rezidüleri üzerinde gerçekleştirilen tek nokta mutasyonlarının protein termostabilitesine olan tahmini etkisi araştırılmıştır. 

Anahtar Kelimeler

• MHC Molekülü,Stabilite,Moleküler Dinamik Simülasyonu,Mutasyon,ENCOM

Kaynakça

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