Investigation for the heritage of a new HLA allele A * 33 ∶88 in a hematopoietic stem cell donor and analysis of its 3D model structure
PEI Yongfeng
LI Hengcong
HUANG Huini
WU Guoguang
Abstract：Objective To investigate the heritage of a novel human leukocyte antigen (HLA) allele A * 33∶88 in a hematopoietic stem cell donor and to analyze its 3D model structure of HLA molecule.Methods One hematopoietic stem cell donor (proband) and their parents were included,and then,5 mL proband and parental venous blood was collected to detect their blood groups of ABO,Rh red blood cells.We took anticoagulated whole blood 200 μL to extract DNA.Subsequently,HLA typing (HLA-A,HLA-B,HLA-DRB1 site typing) was performed using polymerase chain reaction sequencing-based typing (PCR-SBT).The A * 33∶88 protein 3D structure was constructed by the SWISS-MODEL on the basis of taking the HLA-A * 3α chain with the highest homology as the template to construct,after that,we analyzed the 3D structure of the protein.Results The proband and their parents' blood groups were O-type,Rh blood group was D/CcEe,which was consistent with genetic law.The HLA-A genotype of the donor was A * 11 ∶ 01 and A * 33∶88,the HLA-A genotype of the donor's father was A * 33∶03 and A * 33∶ 03,the HLA-A genotype of the donor's mother was A * 11 ∶ 01 and A * 11∶ 01.The difference between A * 33∶88 and A * 33∶03∶01 was in the third exon at position 475 G ＞ A (codon 135 GCG ＞ ACG),and Gla (A) was changed to Thr (T).We compared the 3D model structure between A * 33∶88 and A * 33∶ 03∶ 01.The encoded amino acid at residue 135 was changed from polar non-polar hydrophobic amino acid (A) to polar hydrophilic amino acid (T).The altered amino acid was located at the α-helix (132-178) position of the antigen peptide binding region,which was the side wall of the antigen polypeptide.Conclusions The new allele A * 33∶88 (HWS10022752) is generated from proband father's mutation,which can be passed to his children.According to its 3D model structure,the amino acid substitution is located in α-helices of antigenic peptide-biding region.
Keywords：human leukocyte antigenallelesnovel allele of human leukocyte antigenA * 33∶88human leukocyte antigen gene
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 23-26 )