Characterization of the human leukocyte antigen new alleles A*02: 257 and analysis of its molecular structure model

Abstract

Objective To identify a novel HLA allele, A*24∶257, and to analyze its encoded protein molecular structure modeling. Methods The abnormal HLA-A allele results were initially detected by PCR sequence-based typing (SBT) technique, and then the sample was sequenced again using single allele-specific sequencing strategy to identify the alignments of the novel alleles.Its encoded molecular protein structure were modeled and analyzed with Phyre2 technology as well as RasMol and RCSB PDB Protein Workshop software. Results The single allele-specific sequencing revealed the existence of the new allele sequence which differs from the closest matching allele A*24∶198 by a single nucleotide substitution at position 155 in exon 2 where T->A, which changed the codon 28 from GTG→GAG, resulting in an amino acid exchange with V28→E.Compared with A*24∶02∶01, the new allele has got two amino acid exchanges with V28→E and D29→N.The modeling of the three-dimensional structure of the encoded protein molecule indicates that the Amino acid residues variation is located around the β-turn of the third strand on the bottom of the β pleated sheet of the α1 domain of the molecule, which is close to the end of the central area of the peptide binding groove. Conclusion A novel allele was confirmed by single allele-specific sequencing and the name A*24∶257 has been officially assigned by the WHO HLA Nomenclature Committee.It suggested that the variation of the Amino acid residues may affect the peptide binding and presentation function of the novel A*24: 257 molecule. Key words: Human leukocyte antigen; SBT; Novel allele; Modeling