MART-1 HLA-A2限制性CTL表位的预测

目的 预测黑色素瘤分化抗原ＭＡＲＴ－１的ＨＬＡ－Ａ２限制性细胞毒性Ｔ淋巴细胞（ＣＴＬ）表位。方法 采用超基序与量化基序多项式方案相结合的办法,对目的抗原ＭＡＲＴ－１的ＨＬＡ－Ａ２限制性ＣＴＬ表位进行预测。结果 预测出了６个九肽表位。结论 两种方法预测结果的一致性较好,所预测出的６个ＭＡＲＴ－１的ＨＬＡ－Ａ２限制性ＣＴＬ表位经后续实验筛选,鉴定后,可望用于新型ＭＡＲＴ－１肿瘤治疗性多肽疫苗的设计研究     

液质联用分析肝癌细胞HLA Ⅰ类分子递呈的抗原肽

0 引言HLA-抗原肽是抗原经过抗原递呈细胞(APC)加工后,由HLA分子递呈给T细胞抗原受体(TCR)的短肽. 寻找能够为T细胞所识别的HLA结合肽对于肿瘤免疫学研究及肿瘤有效防治具有重要的理论意义和应用价值,许多国家都在致力于这一领域的研究. 细胞HLA-抗原肽含量很少,分子量很小,难于纯化和测序,是免疫学研究的一个难点. 我们应用肝癌细胞膜酸洗技术及高效液相色谱与质谱联用技术首次分析和鉴定了一条为HLA-A2递呈的肝癌抗原肽.     

An immunohistochemical study of immunological phenomena in minor salivary glands in patients with Sjögren's syndrome

Using different monoclonal antibodies, we performed an immunofluorescent technique on labial salivary glands in order to investigate the immunological phenomena involved in Sjögren's syndrome (SS). An aberrant expression of HLA-DR molecules was detected on cytoplasm of epithelial labial salivary cells in 9 out of 19 (47%) patients, with SS. No such expression was found in 8 patients without SS or in 3 normal controls. HLA-DQ molecules were demonstrated also in two out of ten SS patients without HLA-DR. A lymphocytic infiltration was not correlated with the expression of class II molecules. T cells bearing receptors were not detected. The intracellular adhesion molecules (ICAM-1) and lymphocyte function associated antigen-1 (LFA-1) were not found on epithelial glandular salivary cells of patients and controls. In conclusion, these data suggested that the absence of ICAM-1 and LFA-1 in salivary cells and the absence of infiltrating T cells bearing receptors exclude their immunopathogenetic role in SS; moreover, these data demonstrated that the aberrant expression of HLA class II molecules on epithelial salivary cells of patients with SS is not a phenomenon correlated with the lymphocytic infiltration.     

人类白细胞抗原B27亚型基因与急性前葡萄膜炎的相关性研究

目的 探讨人类白细胞抗原B27亚型基因与急性前葡萄膜炎(acute anterior uveitis,AAU)易感性的关系。 方法 对49例临床确诊的AAU患者,通过聚合酶链反应(polymerase chain reaction, PCR)特异性扩增技术检测B27;以B27阳性者的DNA为模板对其人类白细胞抗原HLA-B的第二、三外显子片段扩增。采用DNA测序技术对扩增产物做基因序列分析,经计算机处理获得受检者HLA-B27亚型的信息。 结果 受检者中29例为B27阳性,占59.39%,其中仅发现B2704(13例,占44.00%)和B27052(16例,占56.00%)二种亚型基因携带者。二者间多数临床表现差异不大,但携带B27052基因的AAU患者伴发强直性脊柱炎(ankylosing spondylitis, AS)的人数(7人,占24.24%)显著高于B2704基因携带者(1人,占3.74%)。 结论 B2704和B27052单独的亚型特异性与AAU无易感性关联;但B27052基因可能与并发AS有关。 (中华眼底病杂志, 1999, 15:139-142)     

Perspectives in transplantation immunology 1991

Summary The clinical success of organ transplantation depends to a large degree on the immunological acceptance of the grafted organ. This paper summarizes from an immunological point of view the recent progress that has been made to improve graft acceptance, and discusses some future aspects in the field. Over the last few years, major emphasis has been put on the development of new immunosuppressive drugs, including FK 506, rapamycin, and Deoxyspergualin. Together with monoclonal antibodies against defined T-cell surface antigens, there are now new and effective means available to prevent or treat rejection episodes. Progress has also been made in the field of HLA typing, where the introduction of molecular biology-based methods significantly increased the accuracy of HLA class II typing. The ultimate goal of transplantation immunology is the induction of (donor-) specific tolerance. While some protocols are effective in inducing peripheral tolerance in experimental animals, these regimens are at present not yet applicable in the clinical situation. To overcome the shortage of donor organs, alternative strategies are currently being considered. Among these, xenotransplantation may eventually prove successful, despite the massive immunological problems such as, e.g., the presence of preformed xenoreactive antibodies.Abbreviations CTL cytolytic T lymphocyte - HLA human leukocyte antigen - MHC major histocompatibility complex - PCR polymerase chain reaction - mAB monoclonal antibody - RFLP restriction fragment length polymorphism - TCR T-cell receptor Preprint of a lecture to be read at the 22nd Congress of the Gesellschaft für Nephrologie, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)     

In vivo induction of HLA molecules in patients with myeloproliferative syndrome during IFNα treatment

Summary Eighteen patients with myeloproliferative syndrome (14 with chronic myeloid leukemia, four with essential thrombocytosis) were investigated for modulation of HLA antigens on peripheral blood lymphocytes, monocytes, and hematopoietic precursors during IFN therapy as a sign of potentially increased immune recognition of malignant cells. After 1 month of IFN therapy, an increased number of monocytes and hematopoietic precursor cells, but not of lymphocytes, expressed HLADQ antigens. In addition, a strong induction of HLA class-I antigens was found on both hematopoietic progenitors and normal peripheral blood mononuclear cells. With daily injections of IFN in the first month of therapy stimulation continuously increased, suggested a major effect of IFNa on hematopoietic progenitors with sustained enhanced expression of HLA class-I antigens during differentiation of myelomonocytic cells. HLA class-I antigen expression was consistently augmented by IFN in all patients, irrespective of their hematological response.This work was supported by theElse Übelmesser Stiftung and theDeutsche Forschungsgemeinschaft, Sonderforschungsbereich 120, projects A3 and D4     

First experiences with HLA-matched corneal grafts in high risk cases

In highly vascularized corneas the number of graft failures caused by irreversible rejections is higher than in non- or slightly vascularized corneas. The importance of antigen compatibility is demonstrated, especially in these high risk cases.Ten highly vascularized corneas were grafted with HLA-matched donor material; only one reversible rejection was seen in this group.Nine non- or slightly vascularized corneas were grafted with donor material chosen at random. Retrospective HLA matching was performed. Three irreversible rejections were seen in this group. The number of HLA incompatibilities was high.     

Induction of carbohydrate‐specific antibodies in HLA‐DR transgenic mice by a synthetic glycopeptide: a potential anti cancer vaccine for human use

Abstract: Over the last few years, anticancer immunotherapy has emerged as a new exciting area for controlling tumors. In particular, vaccination using synthetic tumor‐associated antigens (TAA), such as carbohydrate antigens hold promise for generating a specific antitumor response by targeting the immune system to cancer cells. However, development of synthetic vaccines for human use is hampered by the extreme polymorphism of human leukocyte‐associated antigens (HLA). In order to stimulate a T‐cell dependent anticarbohydrate response, and to bypass the HLA polymorphism of the human population, we designed and synthesized a glycopeptide vaccine containing a cluster of a carbohydrate TAA B‐cell epitope (Tn antigen: α‐GalNAc‐Ser) covalently linked to peptides corresponding to the Pan DR ‘universal’ T‐helper epitope (PADRE) and to a cytotoxic T lymphocyte (CTL) epitope from the carcinoembryonic antigen (CEA). The immunogenicity of the construct was evaluated in outbred mice as well as in HLA transgenic mice (HLA‐DR1, and HLA‐DR4). A strong T‐cell dependent antibody response specific for the Tn antigen was elicited in both outbred and HLA transgenic mice. The antibodies induced by the glycopeptide construct efficiently recognized a human tumor cell line underlying the biological relevance of the response. The rational design and synthesis of the glycopeptide construct presented herein, together with its efficacy to induce antibodies specific for native tumor carbohydrate antigens, demonstrate the potential of a such synthetic molecule as an anticancer vaccine candidate for human use.     

组织相容性复合物DQ基因与胰岛素依赖型糖尿病易感相关性剂量效应规律的研究

为研究中国北方汉族人中组织相容性复合物ＤＱ（ＨＬＡ－ＤＱ）基因与胰岛素依赖型糖尿病（ＩＤＤＭ）遗传易感性相关的剂量效应规律，采用聚合酶链反应和序列特异性寡核苷酸探针杂交技术，对５４例胰岛素依赖型糖尿病患儿和４０例正常成年供血员ＨＬＡ－ＤＱ基因进行了研究。结果：携带４个易感性基因的个体只见于患者，携带３个易感性基因的个体在患者中为３３．３％，正常对照中为１０％；携带２个或１个易感性或保护性基因的个体在正常对照中频率较患者为高，但差异无显著意义；携带３个保护性基因的个体只见于正常对照。提示：ＩＤＤＭ易感性基因具有部分隐性遗传的特点且具有累加效应。个体中１个或２个易感性基因的存在不能对ＩＤＤＭ构成显著的易感性，３个或３个以上易感性基因的存在方可对ＩＤＤＭ构成显著易感性。ＤＱ保护性基因具有部分显性遗传的特点并且也具有累加效应。携带１个或２个保护性基因的个体患ＩＤＤＭ的机会将大大减少，而携带３个保护性基因的个体则可以不发生ＩＤＤＭ。