CYTOTOXIC T CELLS TO CARBOHYDRATE TUMOR ANTIGENS

描述(改编自申请者摘要)：异常 糖基化脂质和蛋白质经常出现在肿瘤中，并且是可识别的 由单抗作为肿瘤相关抗原。最近的观察结果 提示与CD4+有关的碳水化合物特异性细胞免疫 和/或CD8+T细胞可以被诱导，而且碳水化合物是特异的 T细胞具有抗肿瘤活性。在此应用程序中，调查员 描述了一种系统地确定最佳多肽结构的计划 半抗原(TNP或寡糖)可依次与其偶联 诱导针对半胱氨酸的细胞毒性T细胞反应 (低聚糖)部分，不识别肽骨架 它与之共轭的结构。他将决定这是不是 混杂的或独立于呈现抗原的MHC特异性的。他 将通过以下方式评估MHC识别的参与程度 突变型或异型MHC对糖肽的识别 通过评估MHC不依赖于MHC的可能性 半抗原结合物的识别。最后，使用与肿瘤相关的 碳水化合物作为半抗原决定因素，糖肽将被用作 确定是否可以产生显著的肿瘤免疫的免疫原 在小鼠肿瘤模型中使用这种抗原。

DESCRIPTION (Adapted from the Applicant's Abstract): Abnormally glycosylated lipids and proteins often occur in tumors and are identifiable by monoclonal antibodies as tumor-associated antigens. Recent observations suggest that carbohydrate-specific, cell-mediated immunity involving CD4+ and/or CD8+ T-cells can be induced, and that the carbohydrate-specific T-cells can have anti-tumor activity. In this application the investigator describes a plan to systematically determine the optimal peptide structure to which a hapten (either TNP or oligosaccharide can be conjugated, in order to elicit a cytotoxic T-cell response that is specific for the haptenic (oligosaccharide) moiety and that does not recognize the peptide backbone structure to which it is conjugated. He will determine whether that is promiscuous or independent of an antigen-presenting MHC specificity. He will evaluate the extent to which MHC recognition is involved by evaluating the recognition of glycopeptides presented by mutant or allo-MHC specificities, and by evaluating the possibility of MHC-independent recognition of the hapten conjugates. Finally, using tumor-associated carbohydrates as haptenic determinants, glycopeptides will be used as immunogens to determine whether significant tumor immunity can be generated with such antigens in murine tumor models.