Identification and functional perspective of a novel HLA-A allele: A*0279.
A novel HLA-A allele, HLA-A*0279, was identified using PCR-SSP and PCR-SBT methods. It is inheritable. HLA-A*0279 differs from HLA-A*020601 by a single nucleotide at position 497 in exon 3, leading to an amino acid change from Threonine to Isoleucine at the alpha2 helix of HLA molecule. To investigate whether the altered amino acid residue could affect its peptide-binding repertoire, we compared the predicted crystal structure of HLA-A*020601 and HLA-A*0279 by Swiss-PdbViewer software analysis. We found that the crystal structure of the two molecules is very similar except for a difference in the number of hydrogen bonds they can possibly form, which in turn could affect their structural stability. To test whether HLA-A*0279 has the ability to cross-present A*0201 - restricted peptides to T cells, the full lenght cDNA of HLA-A*0201, -A* 020601 and -A*0279 were respectively transfected into COS-7 cells, which were then used as targets in IFN-gamma release Elispot assay. A*2079 was found to be able to present A*0201- restricted peptides to and induce the response of CTL, thus it can be classified as member of the HLA-A2 functional supertype family. This finding would benefit the design of peptide vaccines to be applied in broader populations.
Department of Gastroenterological Surgery, Surgical Oncology Laboratory, People's Hospital, Peking University, 100044, Beijing, People' Republic of China.
Fangfang
F
Liu
Shan
S
Wang
Yingjiang
Y
Ye
Huagang
H
Zhang
Yu
Y
Zhang
Weifeng
W
Chen
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002478:Cells, Cultured; D045142:Cross-Priming; D003461:Crystallography; D005260:Female; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology
D015234:HLA-A Antigens; C512422:HLA-A*02:06:01 antigen; C512421:HLA-A*02:79:01 antigen; D015789:HLA-A2 Antigen; D022223:Vaccines, Subunit