Only in recent years, attentions have been drawn to the significance of expressing killer cell inhibitory receptors (KIR) in T cells KIRs specifically bind to the corresponding region of the MHC class I molecules and ...Only in recent years, attentions have been drawn to the significance of expressing killer cell inhibitory receptors (KIR) in T cells KIRs specifically bind to the corresponding region of the MHC class I molecules and transmit negative signals to prevent cytotoxity of T cells. When the ligands of KIRs are missing, the lysis of the target cells can’t be avoided. Perhaps the existence of KIRs is the main mechanism for preventing T cells from attacking autologous tissues. The recognition mechanism of the interaction between the KIR + donor T cells and the recipient’s MHC class I molecule expressing tissue cells might shed light on the establishment of the immunotolerance for the prevention of allo-graft rejection and graft-versus-host disease.展开更多
基金国家自然科学基金资助项目 (No .30 1 70 395)中国博士后科学基金资助项目 (No .2 0 0 1 - 2 9)
文摘Only in recent years, attentions have been drawn to the significance of expressing killer cell inhibitory receptors (KIR) in T cells KIRs specifically bind to the corresponding region of the MHC class I molecules and transmit negative signals to prevent cytotoxity of T cells. When the ligands of KIRs are missing, the lysis of the target cells can’t be avoided. Perhaps the existence of KIRs is the main mechanism for preventing T cells from attacking autologous tissues. The recognition mechanism of the interaction between the KIR + donor T cells and the recipient’s MHC class I molecule expressing tissue cells might shed light on the establishment of the immunotolerance for the prevention of allo-graft rejection and graft-versus-host disease.
基金supported by R01 grants CA-083859 and CA-100226 (K.S.C.)training grant CA009035-32 (A.K.P.)+1 种基金partially by Centers of Research Excellence grant CA06927 (FCCC) from the National Institutes of Healthsupported in part by an appropriation from the Commonwealth of Pennsylvania
文摘自然杀伤(natural killer,NK)细胞是先天性免疫效应细胞,约占人外周血淋巴细胞总数的10%-15%,主要参与免疫监视,以消除转化细胞和病毒感染细胞。NK细胞最初被界定是由于它们具有自发消除少数主要组织相容性复合物I类(major histocompatibility class I,MHC-I)自身分子表达缺乏细胞的能力,即常说的"丢失自我"识别能力。NK细胞表面表达的MHC-I特异性抑制性受体,可使NK细胞对表达MHC-I的正常细胞耐受,此为丢失自我识别能力的分子基础。由于缺乏抑制性受体的配体,表面MHC-I表达下调的肿瘤细胞和病毒感染细胞易受NK细胞攻击。杀伤细胞免疫球蛋白样受体(KIR;CD158)组成MHC-I结合受体家族,对调节人NK细胞和部分T细胞的活化阈值起重要作用。KIR多样性使NK细胞具有多种功能,在此我们将综述多个水平上的KIR多样性,并诠释KIR多样性是如何影响各种疾病(包括癌症)的易感性的。我们将进一步阐述通过针对KIR进行癌症治疗的策略:利用KIR/MHC-I配体的错配以强化造血干细胞移植的效果,以及通过阻滞KIR以增强对肿瘤细胞的杀伤力。
