HUMAN FC RECEPTOR--ENHANCED ANTIGEN PRESENTATION DEFINED

人类 FC 受体——增强抗原呈递的定义

• 批准号: 2517242
• 负责人: Edmund J Gosselin
• 金额: $ 11.55万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517242
• 关键词: B lymphocyte; T lymphocyte; antibody receptor; antigen antibody reaction; antigen presentation; antireceptor antibody; chimeric proteins; dendritic cells; electron microscopy; flow cytometry; human tissue; immunocytochemistry; immunoglobulin A; immunoglobulin G; interferon gamma; intracellular transport; lymphocyte proliferation; macrophage; monoclonal antibody; monocyte; nitrophenol; protein transport; tissue /cell culture

The guiding hypotheses for this proposal are that enhancement of antigen (Ag) presentation through the interaction of Ag, antibody (Ab) and Fc receptors (FcR): 1) will stimulate active immunity to immunogens, and 2) will vary dependent on the type of FcR or the human Ab isotope involved. FcR-mediated uptake of Ag-Ab complexes can enhance Ag presentation by monocytes at least 100-fold. In addition, recent studies suggest that directing Ag to FcR in vivo may bring out substantial increases in the effectiveness of vaccines. Specific Aim 1 will be to determine which FcR types are most effective at enhancing Ag presentation by monocytes. This will be done by attaching Ag to (Fab')2 or Fab monoclonal Ab (mAb) specific for human FcgammaRI, FCgammaRII, FcgammaRIII (the FcR for IgG) or FcalphaR (the FcR for IgA). Assays will consist of varying numbers of Ag presenting cells, Ag-specific T cells, Ag alone, Ab alone or Ag-Ab conjugates. T cell proliferation and lymphokine production by T cells will be used to measure Ag presentation. Depending on the infectious agent or immunogen involved, the isotope of human Ab produced will vary. Specific Aim 2 will be to define the ability of all human IgG isotopes, and IgA, to participate in enhanced Ag presentation. The hapten NP will be linked to the Ag. Human Fc mouse Fab anti-NP chimeric Ab will be used to create Ag-Ab complexes. Chimeric Ab composed of each of the human IgG isotopes is available and the ratio of NP to Ag will be varied to vary the size of the complex. FcR type- specific mAb will be used as blocking agents to confirm which FcR are being utilized during FcR-enhanced Ag presentation. Human monocytes, macrophages and B cells all express one or more forms of FcR. In addition, B cells have surface immunoglobulin (Ig) which binds Ag and thereby also enhances Ag uptake and subsequent presentation. Dendritic cells are considered to be an important Ag presenting cell as well, although they do not appear to express FcgammaR on their surface. Specific Aim 3 will be to compare the efficiency of receptor-enhanced and non-enhanced Ag presentation among these cell types. These studies will not only improve our understanding of the normal immune response, but will also provide novel approaches for enhancing the effectiveness of vaccines.

该提案的指导假设是抗原的增强 （Ag）通过Ag，抗体（AB）和FC的相互作用表示 受体（FCR）：1）将刺激对免疫原子的主动免疫，2） 将根据涉及的FCR或人类AB同位素的类型而变化。 FCR介导的AG-AB复合物的摄取可以通过 单核细胞至少100倍。 此外，最近的研究表明 将AG引导到体内FCR可能会带来大幅增加 疫苗的有效性。 具体目标1将是确定哪个FCR 类型最有效地通过单核细胞增强AG表现。 这 将通过将Ag附加到（Fab'）2或Fab单克隆AB（mAb）来完成 特定于人fcgammari，fcgammarii，fcgammariii（IgG的FCR） 或fcalphar（IgA的FCR）。 测定将包括不同的数字 Ag呈现细胞，Ag特异性T细胞，单独AG，AB或AG-AB 共轭。 T细胞T细胞的T细胞增殖和淋巴因子产生 将用于测量AG表现。 根据涉及的感染剂或免疫原，不同的同位素 生产的人类AB会有所不同。 具体目标2将是定义 所有人类IgG同位素和IgA的能力，有能力参与增强 AG介绍。 Hapten NP将与AG相关。 人类FC鼠标 Fab抗NP嵌合AB将用于创建AG-AB复合物。 嵌合 由每个人IgG同位素组成的AB可用，比率 NP到Ag的范围将变化，以改变复合物的大小。 FCR类型 - 特定的mAb将用作阻止剂，以确认哪个FCR是 在FCR增强的AG演示过程中被使用。 人的单核细胞，巨噬细胞和B细胞都表达一种或多种形式 fcr。 另外，B细胞具有表面免疫球蛋白（IG） 结合Ag，从而增强了Ag的吸收和随后的呈现。 树突状细胞被认为是重要的AG，作为一个重要的Ag 好吧，尽管它们似乎没有在表面表达fcgammar。 具体目标3将是比较受体增强的效率和 这些细胞类型之间的非增强AG表现。 这些研究不仅会提高我们对正常的理解 免疫反应，但还将提供新颖的方法来增强 疫苗的有效性。

项目成果

Production of genetically engineered biotinylated interleukin-2 and its application in a rapid nonradioactive assay for T-cell activation.

基因工程生物素化白细胞介素 2 的生产及其在 T 细胞激活快速非放射性测定中的应用。

• DOI: 10.1128/cdli.10.3.339-344.2003
• 发表时间: 2003
• 期刊: Clinical and diagnostic laboratory immunology
• 作者: Jordan,RobertA;Preissler,MarkT;Banas,JeffreyA;Gosselin,EdmundJ
• 通讯作者: Gosselin,EdmundJ

Inhibition of interleukin-2 by a Gram-positive bacterium, Streptococcus mutans.

革兰氏阳性菌变形链球菌对白细胞介素 2 的抑制作用。

• DOI: 10.1046/j.1365-2567.1998.00631.x
• 发表时间: 1998
• 期刊: Immunology
• 影响因子: 6.4
• 作者: Plitnick,LM;Banas,JA;Jelley-Gibbs,DM;O'neil,J;Christian,T;Mudzinski,SP;Gosselin,EJ
• 通讯作者: Gosselin,EJ

Expression of HLA-DR (major histocompatibility complex class II) on neutrophils from patients treated with granulocyte-macrophage colony-stimulating factor for mobilization of stem cells.

使用粒细胞巨噬细胞集落刺激因子动员干细胞的患者的中性粒细胞上 HLA-DR（主要组织相容性复合物 II 类）的表达。

• 发表时间: 1995
• 期刊: Blood
• 影响因子: 20.3
• 作者: Mudzinski,SP;Christian,TP;Guo,TL;Cirenza,E;Hazlett,KR;Gosselin,EJ
• 通讯作者: Gosselin,EJ

Use of Nramp2-transfected Chinese hamster ovary cells and reticulocytes from mk/mk mice to study iron transport mechanisms.

使用 Nramp2 转染的中国仓鼠卵巢细胞和 mk/mk 小鼠的网织红细胞研究铁转运机制。

• DOI: 10.1016/j.exphem.2008.04.014
• 发表时间: 2008
• 期刊: Experimental hematology
• 影响因子: 2.6
• 作者: Zhang,An-Sheng;Canonne-Hergaux,Francois;Gruenheid,Samantha;Gros,Philippe;Ponka,Prem
• 通讯作者: Ponka,Prem

Stealth cells: prevention of major histocompatibility complex class II-mediated T-cell activation by cell surface modification.

隐形细胞：通过细胞表面修饰来预防 II 类主要组织相容性复合物介导的 T 细胞激活。

• 发表时间: 1999
• 期刊: Blood
• 影响因子: 20.3
• 作者: Murad,KL;Gosselin,EJ;Eaton,JW;Scott,MD
• 通讯作者: Scott,MD