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DOI :10.26650/B/ET07.2022.012.15   IUP :10.26650/B/ET07.2022.012.15    Full Text (PDF)

An Algorithm Based on HLA Lead Sequence-to-signal Peptide Dimorphism in Human Immunodeficiency Virus Positive Patients and Its Clinical Contributions

Yeliz Öğret, Fatma Savran Oğuz

Human leukocyte antigen (HLA) molecules play an important role in immune responses by interacting with cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells. Classical HLA class I molecules interact with CTLs bearing CD8+ cells in order for the host to discriminate between self and foreign molecules, with evidence for the differentiating effects of the allelic forms of the anti-HLA class I peptide-binding cavity having been found regarding the course of the human immunodeficiency virus type 1 (HIV-1) infection. HLA class I molecules expressed on the cell surface are encoded by exons 2-7. Sequence variation in exons 2, 3, and 4 determine the HLA class I allelic difference. Exon 1 of class I genes encodes a separate leader peptide that is not a structural part of the class I molecule but can be specifically bound and presented by HLA-E. The HLA-A and HLA-C leader sequences are largely invariant and encode methionine (M) at position -21. On the other hand, the HLA-B gene locus (exon 1) has a sequence dimorphism at -21 and gives rise to leader peptides that encode “M” or “T” at the P2 position of the leader sequence. This results in 3 potential genotypes (TT, MT or MM). HLA-B gene products can also be divided into the Bw4 and Bw6 epitope-bearing groups based on variations in the residues at positions 77-83 of the α1 region on the peptide binding pocket. Alternative forms of Bw4 molecules carrying isoleucine (Ile) or threonine (Thr) at position 80 contribute to changes in receptor specificity in T and NK cells.


Keywords: HLA, HIV, HLA-B signal peptide dimorphism, Immunogenetics Database, IMGT
DOI :10.26650/B/ET07.2022.012.15   IUP :10.26650/B/ET07.2022.012.15    Full Text (PDF)

İnsan İmmün Yetmezlik Virüsü Pozitif Hastalarda HLA Lider Dizi-Sinyal Peptid Dimorfizmine Bağlı Olarak Oluşturulan Algoritma ve Klinik Katkısı

Yeliz Öğret, Fatma Savran Oğuz

İnsan lökosit antijeni (HLA) molekülleri, sitotoksik T lenfositler (CTL›ler) ve doğal öldürücü (NK) hücrelerle etkileşerek bağışıklık tepkilerinde önemli rol oynarlar. Klasik HLA sınıf I molekülleri, kendi ve yabancı moleküller arasında konak ayrımı için CD8 taşıyan CTL›ler ile etkileşime girerler. HLA- sınıf I peptid bağlanma oyuğunun alelik formlarının insan immün yetmezlik virüs tip 1 (HIV-1) enfeksiyonu seyri üzerindeki farklı etkilerine dair kanıtlar oluşmuştur. Hücre yüzeyinde ifade edilen HLA sınıf I molekülleri, 2 ila 7 eksonları tarafından kodlanır. Ekson 2, 3 ve 4’teki dizi varyasyonu, sınıf I HLA allellik farklılığı belirler. Sınıf I genlerinin ekson 1’i, sınıf I molekülünün yapısal parçası olmayan, ancak özellikle HLA-E tarafından bağlanabilen ve sunulabilen ayrı bir lider peptidi kodlar. HLA-A ve -C lider dizileri büyük ölçüde değişmezdir ve -21 konumunda metionini (M) kodlar. HLA B gen lokusu ise -21’de bir dizi dimorfizmine sahip olan ekson 1, lider dizinin P2 konumunda ‘’M veya T’yi kodlayan lider peptitlere yol açar. Bu 3 potansiyel genotip ( TT, MT veya MM) ile sonuçlanır: HLA-B gen ürünleri, peptit bağlama cebi üzerindeki α1 bölgesinin 77-83 pozisyonlarındaki kalıntılardaki varyasyona dayalı olarak Bw4 ve Bw6 epitop taşıyan gruplara da ayrılabilir. 80. pozisyonunda izolösin (Ile) veya treonin (Thr) taşıyan Bw4 moleküllerinin alternatif formları, T ve NK hücreleri üzerindeki reseptör spesifikliğinde değişikliklere katkıda bulunur.


Keywords: HLA, HIV, HLA-B Sinyal peptid dimorfizmi, İmmünogenetik Veritabanı, IMGT

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