NATURAL KILLER CELLS MAY RECOGNIZE HLA CLASS I-PEPTIDE COMBINATIONS

自然杀伤(NK)细胞可能识别HLAI类多肽 组合 NK细胞是不会重排或表达的淋巴细胞 免疫球蛋白或T细胞受体基因。NK细胞对病毒的杀伤作用 感染细胞、肿瘤细胞和同种异体细胞 专一性。NK细胞识别靶细胞的机制 目前还不能完全理解。至少有两种机制 NK细胞的杀戮是存在的。一种机制被称为“抗体-- 依赖的细胞毒性“，涉及一种NK膜受体 CD16结合靶标抗体的Fc部分 细胞抗原。第二种杀戮机制不是通过CD16。 这起杀戮是受少校的表情影响的 组织相容性复合体I类分子(在人类中称为人类白细胞抗原 第I类)，通常存在于几乎所有细胞中。在人类白细胞抗原I类中 支持分子α1和α2结构域α螺旋 通过β-褶皱的薄片，形成肽结合槽。Hla 结合的多肽来自于体内合成的蛋白质。 同一间牢房。人类白细胞抗原多肽结合槽残基决定 多肽是结合的。人类白细胞抗原-多肽复合体由T 细胞通过T细胞受体。我们正在研究NK细胞的能力 细胞通过测量识别多肽-人类白细胞抗原I类结合 ~(51)Cr释放试验中的杀伤活性。NK细胞来源 7例健康献血员外周血中掺入~(51)Cr- 已标记的目标细胞。靶细胞为自身的HLAI类细胞 人淋巴母细胞系阴性细胞，721.221，转人白细胞抗原-1 B7普通型，或与人类白细胞抗原-B7单点突变之一。这个 人类白细胞抗原-B7的表达水平由特定的人类白细胞抗原I类决定 和人类白细胞抗原-B7单抗，经标记和分析 荧光激活细胞分选机。到目前为止，已经有27个突变体 测试过。11个显著增加靶细胞的突变体 NK细胞杀伤易感性与普通人群的比较 HLAB7、7型处于与结合体相互作用位置 多肽。这些数据提示NK细胞识别特定的人类白细胞抗原- 多肽复合体，NK细胞可能表达类似的分子 T细胞受体。 关键词：自然杀伤细胞，细胞毒，人类白细胞抗原I类，人类白细胞抗原- B7。

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.