人和猴T淋巴细胞表面TRBC受体及其配体不同于E2分子和CD2的配体

CD2 (E receptor, LFA-3 receptor) and E2 molecules (Bernard, 1988) on human T lymphocytes, CD58 (LFA-3, lymphocyte function associated antigen 3) on human erythrocytes and S14,S42,S110-220 molecules (Bernard, 1987) of sheep erythrocytes are involved in rosette formation of human T lymphocytes with human or sheep erythrocytes. Rosette formation of human and macaque pan-T lymphocytes with tree shrew (Tupaia belangeri) red blood cells (TRBC) (TRBC rosette) has shown different physicochemical properties from that of rosette formation with sheep red blood cells (E rosette) (Ben, 1985). CD2, CD3/TCR complex, CD5, CD6, and CD7 are not involved in TRBC rosette formation (Zheng, 1990). In order to know whether E2, LFA-3,S14,S42 and S110-220 molecules are involved in TRBC rosette formation or human and macaque T lymphocytes, rosette inhibition and antigenic modulation or co-modulation were performed with relevant monoclonal antibodies (McAbs), and hemolytic assay and slide agglutination were also conducted. TRBC rosette formation of human and rhesus monkey PBL was not blocked by E2 McAb (inhibition rate 2.8% and 2.1%, respectively). In contrast, human E rosette formation was obviously blocked at inhibition rate of 49.8% and macaque E rosette formation was slightly inhibited (13.3%). The modulation or co-modulation of E2 molecule with E2 McAb did not affect human TRBC rosette formation. Similar results were shown in rosette formation inhibition of Jurkat cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

人和猴T淋巴细胞表面TRBC受体和E受体的比较研究

TRBC受体不同于已知的全T细胞表面分化抗原CD2,CD3/TCR复合物,CD5,CD6和CD7。CD2分子不参与TRBC玫瑰花结的形成,也不是介导E花结的唯一分子。至少有两个或两个以上蛋白质与TRBC玫瑰花结和E花结的形成有关,其中有的分子为E受体和TRBC受体所共有。因此,很可能有不同于CD2的分子参与了TRBC玫瑰花结的形成。     

人和猴T淋巴细胞表面TRBC受体及其配体不同于E2分子和CD2的配体

T淋巴细胞表面的TRBC受体不同介导E花结形成的E受体(CD2)和E2分子。CD2的配体,人红细胞表面的CD58(LFA-3)和绵羊红细胞表面的T11 TS,S42,S14及S110-220,与TRBC受体的配体无关,TRBC玫瑰花结的形成是通过不同于E花结和人自身玫瑰花结的受体-配体相互作用来实现的,进一步表明,人和猴T淋巴细胞表面和TRBC表面,可能都有独特的蛋白质分子介导TRBC玫瑰花结的形成。     

T淋巴细胞免疫治疗进展

作为肿瘤微环境的重要组成部分, T淋巴细胞在肿瘤的发生、发展中发挥着极其重要的作用,被称为人体内的特种兵。但由于免疫逃逸机制的存在,癌细胞通常会伪装自己,让T细胞无法被识别出,以此躲避人体免疫系统的攻击,那么到底要如何唤醒体内的T细胞来歼灭癌细胞,成为当下肿瘤研究的热点。在过去的几十年,从基础研究到临床应用,诞生了多种基于T淋巴细胞免疫反应的新型抗肿瘤治疗方法,主要有以下三种类型:细胞毒性T淋巴细胞治疗、嵌合抗原受体T细胞治疗以及T细胞受体工程化T细胞治疗。该文简要综述了这三种T细胞免疫治疗的机制、技术与临床应用。     

以T细胞受体为基础的免疫疗法研究进展

T细胞是机体抗肿瘤免疫的核心,以T细胞功能调控为基础的免疫检查点疗法已经在多种肿瘤的临床治疗中取得了重大突破,以基因工程化T细胞为基础的过继性免疫细胞疗法在血液瘤治疗中取得了重要进展,免疫治疗已经对肿瘤的临床治疗产生了深刻变革,成为肿瘤临床治疗策略的重要组成部分。T细胞受体（T cell receptor,TCR）赋予了T细胞识别肿瘤抗原的特异性,能够识别由主要组织相容性复合体（major histocompatibility complex,MHC）呈递的包括胞内抗原在内的广泛肿瘤抗原,具有高度的抗原敏感性,因而具有广泛的抗肿瘤应用前景。2022年第一款TCR药物的上市开启了TCR药物开发的新纪元,多项TCR药物临床研究表现出潜在的肿瘤治疗价值。本文综述了以TCR为基础的免疫治疗策略研究进展,包括T细胞受体工程化T细胞（T cell receptor-engineered T cell,TCR-T）和TCR蛋白药物,以及基于TCR信号的其他免疫细胞疗法,以期为以TCR为基础的免疫治疗策略开发提供参考。     

鸡T细胞受体的研究进展

T细胞受体（TCellReCeptor,TCR）是存在于T细胞膜上的识别外来抗原与自身MHCI类（或Ⅱ类抗原）的复合物成分。它是T细胞将外部信号转化为内部信号,触发T细胞增殖分化、发挥其效应功能的重要分子基础。TCR结构与功能的研究,是深入探讨机体免疫应答机理的重要内容之一。应用单克隆抗体（MCAb）技术和分子生物学技术,已对人和小鼠TCR生物学特性有了详尽的认识。近年来,对鸡TCR结构与功能的研究也取得了新的研究进展,本文就鸡TCR生物学特性的最新研究进展作一综述。一、鸡TCR结构及其亚群分类象哺乳动物一样,鸡TCR多肽键…     

一种新的恒河猴T淋巴细胞活化抗原PTA1

本文应用抗人Ｔ细胞活化抗原ＣＤ２５和ＰＴＡ１ＭｃＡｂ对恒河猴ＰＢＭＣ进行间接免疫荧光染色和流式细胞仪分析,结果发现,恒河猴静止ＰＢＭＣＣＤ２５和ＰＴＡ１均为阴性,而ＰＨＡ活化后或经连续２个月注射ｒＨｕＴＮＦ－α恒河猴ＰＢＭＣ均表达高比率的ＣＤ２５和ＰＴＡ１阳性细胞。此结果表明,ＰＴＡ１抗原可作为恒河猴活化Ｔ淋巴细胞的一种有用标志,为ＰＴＡ１分子结构和功能研究以及采用恒河猴作为灵长类动物模型,观察细胞免疫功能状态提供了有用的资料。     

γδT细胞相关的趋化因子受体

γδT细胞是一群异质性的免疫活性细胞,根据表面标志和功能可将其分为不同亚群。γδT细胞表达的趋化因子受体各异,趋化因子受体的表达与γδT细胞在抗感染、抗肿瘤和自身免疫中的功能发挥密切相关,现就近年来与γδT细胞相关的趋化因子受体研究进展作一综述。     

免疫球蛋白重链可变段和T细胞受体可变段的分子进化研究

为阐明免疫球蛋白(Ig)和T细胞受体(TCR)在抗体多样性产生机理上的异同,作者比较了Ig重链可变段(Ig V_H)和TCR可变段(TCR V)的密码子替代率和协同进化,并分析异同的原因。共搜集8种鼠和3种人的TCR α链可变段(V_α),11种鼠和1种人的TCRβ链可变段(V_β),以及2种鼠和4种人的T细胞γ链可变段;同时搜集11种鼠、3种人、3种南美鳄鱼和1种鲨鱼的Ig V_(H_(o))研究结果揭示:(1)对编码蛋白质的密码子来说,TCR V(包括V_α和V_β)的核苷酸替代率为Ig V_H的2.4倍,说明前者有更高的替代率。(2)以协同进化而言,TCR V和Ig V_H的基因重复率分别为1.7×10~(-6)和1.6×10~(-6)/基因年。两者几乎相同,均系低速保持者。TCR V的数目(V_α为100,V_β为30)远少于Ig V_H(数目为300),原因是前者受到主要组织相容性复合体的制约,即受到负选择,这与中性学说观点相一致。文章还讨论了体细胞突变和DNA重排对两类抗体多样性产生上的作用,并探讨了IgV_H和TCR V的假基因问题。     

A receptor for IgA on human T lymphocytes.

Receptors for IgA antibody-antigen complexes were demonstrated on 2 to 18% (mean 6.7%) of human peripheral blood T cells. The proportion of cells bearing detectable IgA receptors was low in freshly prepared T cells and increased in number after 18 to 24 hr of culture similar to the time course of appearance of the Tmu receptor. These T receptors were shown to be distinctly different from Fc-IgM and Fc-IgG receptors on T cells by blocking studies with purified IgA, IgG, and IgM.     

Desferoxamine blocks IL 2 receptor expression on human T lymphocytes

Thymidine uptake by PHA-stimulated human lymphocytes is reduced in the presence of 100 microM or greater concentrations of the iron-chelating agent desferoxamine (DF). We assessed expression of IL 2 receptor, 4F2 and Ia antigens, IL 2 production, and cell cycle progression by blood mononuclear cells (MNC) stimulated by PHA in the presence or absence of DF to determine whether the lack of T cell proliferation was a manifestation of inhibition of an earlier activation event. Tac antigen expression on PHA-stimulated MNC was inhibited by DF throughout 8 days of culture, and those cells which were positive had a low density of Tac antigen as compared with controls without DF. Expression of other activation antigens, 4F2 and Ia, was not impaired by DF. The supernatants of the DF-containing and control cultures contained equivalent IL 2 activity, as measured on the HT-2 cell line. Cell cycle analysis of these cultures shows that the addition of DF at the beginning of culture blocks most cells from undergoing G0 to G1 transition, whereas later addition of DF arrests the progression of the T cell blasts through the cell cycle. Separation of cells cultured with PHA and DF into Tac+ and Tac- subsets showed that progression from G0 to G1 was restricted to the former subset. These results suggest that interference with IL 2 receptor expression might contribute to the block in mitogen-induced proliferation caused by DF.     

Rosetting of human T lymphocytes with sheep and human erythrocytes. Comparison of human and sheep ligand binding using purified E receptor

Previous studies have shown that the purified T lymphocyte glycoprotein, cluster differentiation 2 (CD2) (also known as T11, lymphocyte function-associated antigen (LFA)-2, and the erythrocyte (E) rosette receptor) interacts with the LFA-3 molecule on human E. We have examined the interaction of the purified CD2 molecule with the T11 target structure (T11TS) molecule on sheep E, and compared the two interactions. Purified, 125I-labeled CD2 bound to sheep E and the binding was inhibited by anti-T11TS monoclonal antibody (mAb). Reciprocally, the binding of T11TS mAb to sheep E was inhibited by pretreatment of sheep E with purified CD2. High concentrations of purified CD2 aggregated sheep E, possibly by inserting into the membrane, and the aggregation was inhibited by T11TS mAb. The affinity and number of binding sites for purified CD2 on sheep and human E was found to be similar, with Ka of 9 X 10(7)/M and 6 X 10(7)/M and 9800 and 8300 CD2 binding sites/E, respectively. Thus, the human T lymphocyte CD2 molecule is a receptor that cross-reacts between LFA-3 on human E and T11TS on sheep E, suggesting that LFA-3 and T11TS are functionally homologous ligands. As measured by saturation mAb binding, there are 8100 and 3900 ligand molecules/sheep and human E, respectively. Human and sheep E have surface areas of 145 and 54 micron 2, respectively. The 3.2- to 5.6-fold higher ligand density on sheep E appears to account for the ability of sheep but not human E to rosette with certain types of human T lymphocytes.     

Antigen-dependent regulation of interleukin 2 receptor expression on cloned human cytotoxic T lymphocytes

IL 2 receptor expression as a function of time after antigenic stimulation was examined on antigen-dependent human CTL clones specific for type A influenza virus. The anti-Tac monoclonal antibody was used to follow IL 2 receptor levels on the cloned cells. Shortly after antigenic stimulation, IL 2 receptor expression was maximal; by 1 wk, however, levels had decayed considerably, and by 2 wk only background expression remained. Reexpression of IL 2 receptors could be induced by exposure of quiescent clones to antigen or lectin. IL 2-driven proliferation of the cytotoxic clones was also examined, and it decayed with the same kinetics as IL 2 receptor levels. Proliferation of quiescent cells could also be obtained by antigen-specific stimulation. Thus, IL 2 receptor expression by human CTL clones at least in part regulates the antigen-specific proliferation of these cells.     

Simultaneous increased expression of E-rosette receptor (CD2, T11) and T cell growth factor receptor on human T lymphocytes during activation

The E-rosette receptor (CD2, T11) is a differentiation antigen expressed on immature and mature human T lymphocytes. Activation of T cells from human peripheral blood with phytohemagglutinin (PHA) or with monoclonal antibody to the CD3-Ti complex (anti-Leu-4) caused the expression of CD2 to increase 10- to 20-fold. Dual parameter correlated analyses with antibody to the T cell growth factor (TCGF) receptor (anti-Tac) and anti-CD2 antibody demonstrated that the increase in CD2 expression occurred at the same time and on the same cells that expressed the TCGF receptor after stimulation with PHA. The increased expression of CD2 and the initial expression of Tac were totally inhibited by cycloheximide, but were not affected by sufficient actinomycin-D to block the T cell proliferative response. The expression of CD2 was compared with the expression of CD4 and CD8, i.e., T cell differentiation antigens on cytotoxic/suppressor or helper T cells, respectively. Although virtually all of the small percentage of freshly isolated Tac+ peripheral blood cells belonged to the CD4+, CD8- subset, both CD4+ and CD8+ T cells were equivalently activated by PHA to express Tac. By 20-30 hr after activation, the expression of CD4 or CD8 was initially decreased 10-50%. Subsequently, the expression of CD4 and CD8 returned to the levels on resting T cells but did not increase further. Therefore, the increase in CD2 expression does not reflect a universal property of cell surface antigens on activated T lymphocytes.