NATURAL KILLER CELLS MAY RECOGNIZE HLA CLASS I-PEPTIDE COMBINATIONS

自然杀伤细胞可能识别 HLA 类 I 肽组合

• 批准号: 3775601
• 负责人: Zoya B Kurago
• 金额: --
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3775601
• 关键词: MHC class I antigen; T cell receptor; antigen presentation; cell mediated cytotoxicity; flow cytometry; human tissue; major histocompatibility complex; membrane proteins; monoclonal antibody; natural killer cells; point mutation; radiotracer; transfection

NATURAL KILLER (NK) CELLS MAY RECOGNIZE HLA CLASS I-PEPTIDE COMBINATIONS NK cells are lymphocytes that do not rearrange or express immunoglobulin or T cell receptor genes. NK cells kill virally infected cells, tumor cells, and allogeneic cells with broad specificity. The mechanisms of target cell recognition by NK cells are currently not entirely understood. At least two mechanisms of killing by NK cells exist. One mechanism is called "antibody- dependent cytotoxicity", which involves an NK membrane receptor CD16 binding the Fc portion of an antibody specific for a target cell antigen. The second mechanism of killing is not via the CD16. This killing is affected by the expression of the major histocompatibility complex class I molecules (in humans called HLA class I), normally present on nearly all cells. In HLA class I molecules alpha 1 and alpha 2 domain alpha helices are supported by a beta-pleated sheet, forming the peptide binding groove. HLA bound peptides are derived from proteins synthesized inside the same cell. HLA peptide binding groove residues determine which peptides are bound. HLA-peptide complexes are sampled by the T cells via the T cell receptor. We are studying the ability of NK cells to recognize peptide-HLA class I combinations by measuring the killing activity in 51Cr-release assays. NK cells from peripheral blood of 7 healthy human donors are mixed with 51Cr- labeled target cells. The target cells are self-HLA class I negative human lymphoblastoid cells, 721.221, transfected with HLA- B7 common type, or with one of HLA-B7 single point mutants. The levels of HLA-B7 expression are determined by specific HLA class I and HLA-B7 monoclonal antibodies, labeled and analysed by fluorescence activated cell sorter. 27 mutants have so far been tested. Of 11 mutants that significantly increased target cell susceptibility to killing by NK cells in comparison with the common type HLA-B7, 7 are in the position to interact with the bound peptide. These data imply that NK cells recognize specific HLA- peptide complexes, and that NK cells may express a molecule similar to the T cell receptor. Key words: natural killer cells, cytotoxicity, HLA class I, HLA- B7.

自然杀伤细胞（NK）可识别HLA I类肽 组合 NK细胞是不重排或表达 免疫球蛋白或T细胞受体基因。NK细胞杀死病毒 感染的细胞、肿瘤细胞和具有广泛的 的特异性NK细胞识别靶细胞的机制 目前还没有完全理解。至少有两种机制 存在NK细胞的杀伤。一种机制叫做“抗体- 依赖性细胞毒性”，其涉及NK膜受体 CD 16结合靶特异性抗体的Fc部分 细胞抗原第二种杀伤机制不是通过CD 16。 这场杀戮受到了少校的表情影响 组织相容性复合物I类分子（在人类中称为HLA I类），通常存在于几乎所有细胞上。HLA I类 支持分子α 1和α 2结构域α螺旋 通过β折叠片形成肽结合沟。HLA 结合肽来源于在细胞内合成的蛋白质， 相同单元HLA肽结合沟残基决定 肽被结合。HLA-肽复合物由T 通过T细胞受体。我们正在研究NK的能力 细胞识别肽-HLA I类组合， 在51 Cr释放测定中的杀伤活性。NK细胞 将7名健康人供体的外周血与51 Cr- 标记的靶细胞。靶细胞为自身HLA I类 阴性人淋巴母细胞样细胞，721.221，用HLA- B7共同型或HLA-B7单点突变型。的 HLA-B7表达水平由特异性HLA I类决定 和HLA-B7单克隆抗体，标记和分析， 荧光激活细胞分选仪。到目前为止已经有27个变种人 测试.在11种突变体中， 与普通的NK细胞相比， 型HLA-B7，7处于与结合物相互作用的位置。 肽。这些数据意味着NK细胞识别特定的HLA- 肽复合物，并且NK细胞可以表达类似的分子。 与T细胞受体相连 关键词：自然杀伤细胞，细胞毒性，HLA I类，HLA- B7.