title: Functional supertype of HLA-A2 in the presentation of Flu matrix p58-66 to induce CD8+ T-cell response in a Northern Chinese population.
abstract: The functional supertype of HLA-A2 was investigated in the presentation of the A*0201-restricted Flu matrix p58-66 peptide to activate recall CD8+ T-cell response. In healthy Northern Chinese, the HLA-A2 supertype was mainly composed of the six alleles, A*0201 (26.4%), A*0206 (12.7%), A*0203 (8.2%), A*0207 (7.3%), A*0210 (1.8%) and A*0205 (0.9%), as analyzed by PCR using sequence specific primer (PCR-SSP) and sequence based typing (SBT). The IFN-gamma release Elispot assay was employed to assess effector CD8+ T cells. In A*0201-bearing individuals, the CD8+ T-cell response was potent when stimulated with autologous CD8- PBMCs. The frequency of the effector CD8+ T cells was 96.6% with the magnitude of effector CD8+ T cells of 225 SFC/5 x 104 CD8+ T cells and the RI of 25.7. In non-A*0201 individuals, the effector CD8+ T cells were minimally detectable while the peptide was presented by the autologous CD8- PBMCs. However, the induction of the response of CD8+ T cells obtained from non-A*0201 individuals was remarkably improved when the peptide was presented by autologous dendritic cells instead of CD8- PBMCs. The HLA-A2 alleles possessing cross-reactivity in the peptide presentation were mainly of A*0206 and non-A*0201 heterozygotes of A*0206 and A*0210. Moreover, A*0206 as the HLA-A2 functional supertype was further confirmed by tetramer assay. In two A*0206+ donors with CD8+ T-cell response to the peptide, the CD8+ T-cell frequency assessed by specific binding of peptide HLA-A*0201 tetramer was 4.62% and 1.66%, respectively. Thus, our results have substantiated the immunological relevance of the HLA-A2 supertype, which may benefit the design of peptide vaccines with the potential to be applicable in broader populations.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: H-G
authors.initials: HG
authors.lastname: Zhang
authors.forename: X-W
authors.initials: XW
authors.lastname: Pang
authors.forename: X-Y
authors.initials: XY
authors.lastname: Shang
authors.forename: Q
authors.initials: Q
authors.lastname: Xing
authors.forename: W-F
authors.initials: WF
authors.lastname: Chen
mesh_terms: D000483:Alleles; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002681:China; D003713:Dendritic Cells / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; C448634:influenza matrix peptide (58-66); D007371:Interferon-gamma