ITAM两步磷酸化基础上的TCR识别模型

将T细胞受体(TCR)的活性与免疫酪氨酸受体激活基序(ITAM)活性联系起来，深入考虑了TCR与其配体的亲和力和离解率．结果表明抗原多肽上信号氨基酸部分的细小差别，将有效地引起截然不同的T细胞应答反应．发生在T细胞应答早期信号事件中的TCR与其配体的亲和力和离解率参与决定了最终的T细胞应答结果．     

T细胞共刺激信号系统研究进展

T细胞是获得性免疫应答的主要识别和效应细胞．T细胞的活化需要两种信号同时存在（即双信号模型，two-signal model）：一是由T细胞受体（TCR）与MHC-抗原肽复合物介导的第一信号，该信号决定了T细胞抗原应答的特异性；二是由表达于T细胞表面的膜蛋白分子及其配体介导的共刺激信号，该信号对于T细胞识别抗原后的完全活化是必须的．共刺激分子的发现为调控T细胞活化及其介导的免疫反应提供了新策略．     

T细胞共刺激信号系统研究进展

T细胞是获得性免疫应答的主要识别和效应细胞．T细胞的活化需要两种信号同时存在（即双信号模型，two-signal model）：一是由T细胞受体（TCR）与MHC-抗原肽复合物介导的第一信号，该信号决定了T细胞抗原应答的特异性；二是由表达于T细胞表面的膜蛋白分子及其配体介导的共刺激信号，该信号对于T细胞识别抗原后的完全活化是必须的．共刺激分子的发现为调控T细胞活化及其介导的免疫反应提供了新策略．     

CD28分子的研究进展

目前大量实验已证明,CD28家族分子与B7家族分子结合后产生的共刺激信号,即第二信号在免疫应答的T细胞激活中起重要作用.CD28与B7两种分子的相互作用可产生一个特殊的协同刺激使TCR介导的抗原识别信号导致细胞的活化而不是无能,现就CD28家族分子的结构、配体、信号传导以及对免疫应答的调控作一综述.     

中药免疫增强剂研究进展

中药免疫增强剂能非特异性地与抗原结合而增强其特异性免疫原性,调节、增强、恢复机体免疫功能,增强机体免疫应答或改变免疫应答类型,是治疗和预防疾病的重要物质,特别是对疫苗发挥作用具有独特的效果。详细论述了中药免疫增强剂的种类、有效成分及影响其作用功能的因素等。     

抗体生产中佐剂的选择和应用

当某些物质与抗原一起注入机体内,能增强机体对抗原的特异性体液和细胞调节的免疫应答,这些物质称为免疫佐剂(Immuno adjuvant),简称佐剂。免疫佐剂能够非特异地提高机体对弱免疫原性的特异抗原的免疫应答或改变免疫反应类型。当佐剂与抗原物质混合注入机体后,可形成抗原储存库     

T细胞对抗原的识别：中国科学家谈科学

T细胞对抗原的识别是抗原特异性免疫反应的基础。它可使机体获得保护性的抗原特异性免疫应答，对揭示免疫应答的规律、阐明免疫相关疾病的发生机制、寻找有效的治疗方法有重要意义。     

日本血吸虫病人群同种型抗体应答的特征及其流行病学意义

该研究通过对我国日本血吸虫病流行区人群的免疫流行病学调查,确定年龄相关的优势血吸虫抗原特异性抗体应答的同种型特征及与化疗后再感染状态相关的优势血吸虫特异性抗体应答的分子机理,进而确定其抗原特异性,为日本血吸虫病免疫流行病学研究和疫苗的研制提供基本信息.     

淋巴细胞的发育、分化、激活、凋亡及其调节——中国科学家谈科学

淋巴细胞的发育、活化及凋亡的研究，有助于深化对特异性免疫应答及调节机理的认识。对淋巴细胞生命过程的干预可望为免疫缺陷、自身免疫、感染和肿瘤等疾病的预防及治疗提供新的、更有效的方法。     

流动注射免疫比浊法测定血清中IgA

1引言 免疫球蛋白是具有抗体活性、能与相应抗原呈特异性结合的蛋白质,普遍存在于体液、组织液及外分泌液中,在免疫应答中产生重要作用.     

A motif in the alphabeta T-cell receptor controls positive selection by modulating ERK activity

Positive selection allows thymocytes that recognize an individual's own major histocompatibility complex (self-MHC) molecules to survive and differentiate, whereas negative selection removes overtly self-reactive thymocytes. Although both forms of thymic selection are mediated by the alphabeta T-cell receptor (TCR) and require self-MHC recognition, an important question is whether they are controlled by distinct signalling cascades. We have shown that mutation of an essential motif within the TCR alpha-chain-connecting peptide domain (alpha-CPM) profoundly affects positive but not negative selection. Using transgenic mice expressing a mutant alpha-CPM TCR we examined the contribution of several mitogen-activated protein kinase (MAPK) cascades to thymic selection. Here we show that in thymocytes expressing a mutant alpha-CPM receptor, a positively selecting peptide failed to activate the extracellular signal-regulated kinase (ERK), although other MAPK cascades were induced normally. The defect in ERK activation was associated with impaired recruitment of the activated tyrosine kinases Lck and ZAP-70, phosphorylated forms of the TCR component CD3zeta and the adaptor protein LAT to detergent-insoluble glycolipid-enriched microdomains (DIGs). Therefore, an intact DIG-associated signalosome is essential for sustained ERK activation, which leads to positive selection.     

T细胞对不同配体的鉴别模型

T淋巴细胞对抗原多肽的免疫应答是免疫系统的重要事件,T细胞对于分辨不同的MHC－pep复合物有着不同寻常的能力,抗原多肽上信号氨基酸部分的细小判别,将有效的引起截然不同的T细胞响应,有些可以激活T细胞,而另外一些却抑制了细胞的活化,此模型深入考虑了PTK的活性及TCP与其配体的亲和力,将早期信号事件与决定了T细胞活化的持续信号联系了起来,为T细胞对不同配体的免疫应答提供了一个合理的理论解释。     

Two tyrosines in CD3ε-ITAM are required to induce T lymphocyte apoptosis

CD3ε of T cell antigen receptor complex (TCR/CD3) plays an important role in the resembling of the complex and activation signaling through its conservative immunoreceptor tyrosine-based activation motif (ITAM) in the cytoplasmic tail. Previous study showed that a chimera molecule, consisting of the extracellular-transmembrane domain of human CD8α fused to the cytoplasmic domain of CD3ε, induced apoptosis of T lymphocytes, indicating that apoptotic signals were transduced through the CD3ε- ITAM. To elineate involvement of the two tyrosines in apoptotic signaling pathway, cDNAs with mutations at Y170F, Y181F and Y170F/Y181F in CD8-ε-ITAM were made by point mutation and PCR, and then cloned into pcDNA3 eukaryotic expression vectors. Stable expression cell lines were established after transfection of the expression vectors into CD8+- Jurkat T lymphocytes. Stimulation of these cell lines with anti-CD8 monoclonal antibody showed that only the cells with expression of wild type chimera CD8-ε died by apoptosis, but not those cells with expressions of mutated CD8-ε chimera, indicating that the two tyrosines in CD3ε-ITAM were required for the apoptotic signal transduction in T lymphocytes.     

Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity

Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10-Malt1-mediated NF-kappaB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10-Malt1. Thus, our results define a novel innate immune pathway and indicate that evolutionarily distinct ITAM receptors in innate and adaptive immune cells use diverse adaptor proteins to engage selectively the conserved Bcl10-Malt1 module.     

T-cell receptors of human suppressor cells

Cells which can suppress the immune response to an antigen (TS cells) appear to be essential for regulation of the immune system. But the characterization of the TS lineage has not been extensive and many are sceptical of studies using uncloned or hybrid T-cell lines. The nature of the antigen receptor on these cells is unclear. T cells of the helper or cytotoxic lineages appear to recognize their targets using the T-cell receptor (TCR) alpha beta-CD3 complex. TCR beta-gene rearrangements are also found in some murine and human suppressor cell lines but others have been shown not to rearrange or express the beta-chain or alpha-chain genes. We previously established TS clones derived from lepromatous leprosy patients which carry the CD8 antigen and recognize antigen in the context of the major histocompatibility complex (MHC) class II molecules in vitro. We here report the characterization of additional MHC-restricted TS clones which rearrange TCR beta genes, express messenger RNA for the alpha and beta chains of the TCR and express clonally unique CD3-associated TCR alpha beta structures on their cell surface but do not express the gamma chain of the gamma delta TCR on the cell surface. We conclude that antigen recognition by at least some human CD8+ suppressor cells is likely to be mediated by TCR alpha beta heterodimers.     

Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions

The majority of T cells bear the T-cell receptor (TCR) alpha beta complex which recognizes foreign antigen peptides only in the context of self major histocompatibility complex (MHC) molecules. Such T cells function in a variety of effector roles and secrete cytokines that mediate the activation and differentiation of other cells in the immune system. Recently, a small subpopulation T cells was found to bear a distinct TCR composed of gamma and delta subunits. In man, TCR gamma delta+ cells are distributed as approximately 5 per cent of the CD3+ cells in all organized lymphoid organs as well as in the skin- and gut-associated lymphoid tissues. Although a limited number of germ-line genes encode the TCR gamma and delta subunits, extensive junctional variation particularly in the delta gene, results in unprecedented diversity for this receptor. The nature of the specificity and immunological functions of these T cells remains enigmatic. We report here that in contrast to the normal low frequency of gamma delta-bearing cells in lymphoid tissues, peripheral blood, or normal skin, the frequency is increased five to eightfold in particular granulomatous reactions of leprosy. TCR gamma delta+ lymphocyte lines from these leprosy skin lesions proliferate in vitro specifically to mycobacterial antigens. This reactivity to foreign antigens appears to require presentation in the context of self-molecules. Moreover, culture supernatants from activated gamma delta T lymphocytes induce adhesion and aggregation of bone-marrow monocytes in the presence of granulocyte monocyte-colony stimulating factor (CSF), suggesting that products of gamma delta-bearing T cells may play a role in the immune response, possibly by stimulating granuloma formation.     

Abnormal tyrosine phosphorylation on T-cell receptor in lymphoproliferative disorders

The study of human autoimmune diseases has benefited greatly from analysis of animal models. Mice that are homozygous for either the lpr (lymphoproliferation) or gld (generalized lymphoproliferative disease) mutant genes develop a disease characterized by massive lymphadenopathy and autoantibody formation. With age, the lymphoid organs in these mice are replaced with a greatly expanded population of abnormal lymphocytes. Recent work has shown that these cells are likely to be in the T-cell lineage. They rearrange and transcribe the genes for the alpha and beta subunits of the T-cell receptor (TCR) and a third, T-cell receptor-like gene, T gamma. As determined by immunofluorescence with anti-receptor antibodies the cells also express TCR on the cell surface. The murine T-cell receptor consists of the alpha and beta chains, derived from the rearranged alpha and beta genes, in non-covalent association with seven other chains; the delta chain, of relative molecular mass (Mr) 26,000 (26K), the epsilon chain (25K), a glycosylated 21K chain (gp21) which is probably the homologue of the gamma chain of T3 (CD3), a 16K homodimer (zeta) and a 21K dimer (p21). This multichain complex is thought to be the murine analogue of the human T3 complex. After activation of normal T cells by antigen or lectin, p21 is phosphorylated on tyrosine residues and gp21 is phosphorylated on serine residues. In contrast, in the gld and lpr cells, p21 is phosphorylated even in the absence of antigen or lectin, whereas gp21 is not phosphorylated.     

Intrathymic signalling in immature CD4+CD8+ thymocytes results in tyrosine phosphorylation of the T-cell receptor zeta chain

Thymic selection of the developing T-cell repertoire occurs in immature CD4+CD8+ double-positive thymocytes and is thought to be mediated by signals transduced by T-cell antigen receptor (TCR) molecules and possibly by CD4 and CD8 accessory molecules as well. It is not known, however, which signal-transduction mechanisms function in immature CD4+CD8+ thymocytes on engagement of TCR, CD4 or CD8 molecules. In mature T cells, CD4 and CD8 molecules are each associated with the src-like protein tyrosine kinase p56 lck and signals transduced by TCR and CD4 activate tyrosine kinases that phosphorylate TCR-zeta chains and other intracellular substrates. Consequently, we examined whether tyrosine kinases could be similarly activated in immature CD4+CD8+ thymocytes. Unexpectedly, we found that TCR-zeta chains from CD4+CD8+ thymocytes were already phosphorylated in vivo, and that dephosphorylation of this TCR subunit occurred on removal of CD4+CD8+ cells from their intrathymic environment. Rephosphorylation of TCR-zeta in cultured CD4+CD8+ thymocytes occurred rapidly in vitro, either in response to cross-linking of TCR, CD4 or CD8 by specific monoclonal antibodies, or on cell-cell contact. These observations indicate that tyrosine kinases are activated in vivo in immature CD4+CD8+ thymocytes undergoing thymic differentiation and selection. They also indicate that TCR, CD4 and CD8 molecules can function in CD4+CD8+ thymocytes as signalling molecules to activate tyrosine kinases and that phosphorylated TCR-zeta serves as a marker of these signalling events.     

Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase

Cbl is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface. The evolutionarily conserved amino-terminal region of Cbl (Cbl-N) binds to phosphorylated tyrosine residues and has cell-transforming activity. Point mutations in Cbl that disrupt its recognition of phosphotyrosine also interfere with its negative regulatory function and, in the case of v-cbl, with its oncogenic potential. In T cells, Cbl-N binds to the tyrosine-phosphorylated inhibitory site of the protein tyrosine kinase ZAP-70. Here we describe the crystal structure of Cbl-N, both alone and in complex with a phosphopeptide that represents its binding site in ZAP-70. The structures show that Cbl-N is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium-binding domain, and a divergent SH2 domain that was not recognizable from the amino-acid sequence of the protein. The calcium-bound EF hand wedges between the 4H and SH2 domains and roughly determines their relative orientation. In the ligand-occupied structure, the 4H domain packs against the SH2 domain and completes its phosphotyrosine-recognition pocket. Disruption of this binding to ZAP-70 as a result of structure-based mutations in the 4H, EF-hand and SH2 domains confirms that the three domains together form an integrated phosphoprotein-recognition module.