Yang J C, Perry-Lalley D
Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA.
J Immunother. 2000 Mar-Apr;23(2):177-83. doi: 10.1097/00002371-200003000-00001.
Recently, significant progress has been made in identifying specific tumor-associated antigens recognized by T cells and defining the specific peptide epitopes within these proteins that are processed and presented on class I major histocompatibility antigens. Most of these antigens have been identified in human melanoma, where many of them appear to be tissue-specific, nonmutated proteins expressed by melanoma and normal melanocytes but not by other tissues. There has been much less progress in identifying the tumor antigens on murine tumors that are recognized by T cells, and this has restricted the development of preclinical animal models for immunotherapy. The authors previously described a method for generating tumor-reactive T cells from murine tumors (tumor infiltrating lymphocytes) that are CD8+ T cells recognizing autologous tumor and that can inhibit established tumor on adoptive transfer. Here the authors show that the envelope protein of an endogenous murine retrovirus of the AKV family, found in the germline of the C57BL/6 mouse, is recognized by tumor-infiltrating lymphocytes from two histologically different tumors syngeneic to that mouse strain. Furthermore, the authors identify the specific 9-amino acid peptide from the p15E transmembrane component of this envelope protein that is recognized in the context of major histocompatibility complex Kb, show that it is naturally presented and recognized on several other H-2b tumors, and that cytotoxic T lymphocytes specific for this epitope are therapeutic for these antigen-expressing tumors on adoptive transfer.
最近，在识别T细胞识别的特定肿瘤相关抗原以及确定这些蛋白质中经加工后呈递于I类主要组织相容性抗原上的特定肽表位方面取得了重大进展。这些抗原大多是在人类黑色素瘤中发现的，其中许多似乎是黑色素瘤和正常黑素细胞表达的组织特异性、未突变的蛋白质，而其他组织不表达。在识别小鼠肿瘤上被T细胞识别的肿瘤抗原方面进展要少得多，这限制了免疫治疗临床前动物模型的发展。作者之前描述了一种从鼠肿瘤（肿瘤浸润淋巴细胞）中产生肿瘤反应性T细胞的方法，这些细胞是识别自体肿瘤的CD8 + T细胞，在过继转移时可抑制已形成的肿瘤。在此，作者表明，在C57BL / 6小鼠种系中发现的AKV家族内源性鼠逆转录病毒的包膜蛋白，被来自与该小鼠品系同基因的两种组织学不同肿瘤的肿瘤浸润淋巴细胞识别。此外，作者从该包膜蛋白的p15E跨膜成分中鉴定出特定的9个氨基酸肽，该肽在主要组织相容性复合体Kb的背景下被识别，表明它在其他几种H-2b肿瘤上自然呈递并被识别，并且针对该表位的细胞毒性T淋巴细胞在过继转移时对这些表达抗原的肿瘤具有治疗作用。
