The influence of histo-blood group I antigen on leukemia cells against NK cell cytotoxicity

• Main Authors: Yen-Hua Lee, 李彥樺
• Other Authors: Yuh-Ching Twu
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/z9k7rb

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 103 === The I and i antigens, carried on glycolipids and glycoproteins, were first identified on human red blood cells (RBCs). The chemical determinant of histo-blood group I/i antigens is solely on branched and straight poly-LacNAc, respectively. By the activity of I -1,6-N-acetyllactosaminyltransferase (I  6GlcNAcT, also designated IGnT), the straight poly-LacNAc backbone can also be branched by additions of N-acetyllactosamine on the 6-position of some galactose units, thus forming the I-branching structures. In addition, anti-I can be detected in the serum of patients with autoimmune hemolytic anemia, and it’s one of the important cold aggultinin in transfusion. Moreover, many studies support the idea that altered expression levels of Ii antigens and its terminal glycans, such as sLewisa and sLewisx, were correlated with oncogenesis and metastasis. However, the mechanism needs further investigation. Our hypothesis is that the branched I antigens of the leukemia cells might involve the escape from the natural killer (NK) cell-mediated immune surveillance. First, we examined the IGnT transcripts and surface I antigens of the human leukemia cell lines by performing real-time PCR and FACS analysis, respectively. Interestingly, we found that the Raji cells, which expressed highly amount of I antigens, possessed more sensitivity to NK-92MI-mediated killing by using the non-radioactive cytotoxicity assay. To investigate the correlation between the I antigen and the sensitivity of the NK-mediated cytotoxicity, we overexpressed IGnTA in the MEG-01 cells, which expressed undetectable level of I antigen, for the establishment of the I-expressed MEG-01 cell model. According to our data, the branched I antigen of the leukemia cells enhanced the susceptibility of target cell to NK-92MI-mediated cytotoxicity. However, the increasing level of I antigen did not enhance the NK-target interaction in the conjugate formation assay. And the raising susceptibility of leukemia cells to cytotoxicity was not through increasing secretion of granzyme-B, which was released by NK cells in the degranulation. In this study, we have provided the evidence that I expression level of leukemia cells are highly correlated to the susceptibility to NK-mediated cytotoxicity. More and more studies have demonstrated that NK-based therapy showed the potential to treat highly risk leukemia with adverse reaction. Therefore, the understanding of the effect and mechanism(s) of I antigen on leukemia cells against NK-mediated killing might improve the outcome of current immunotherapy.