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MHC Class I Antigen Presentation in Viral Infections

病毒感染中 MHC I 类抗原呈递

基本信息

批准号：
7991835
负责人：
Luis J Sigal
金额：
$ 41.94万
依托单位：
RESEARCH INST OF FOX CHASE CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-06-01 至 2012-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7991835
关键词：
Abbreviations Accounting Acute Disease Address Affect Amino Acids Antibodies Antigen Presentation Antigen-Presenting Cells Antigens Antiviral Response Binding Blood Blood Circulation Bone Marrow CD8-Positive T-Lymphocytes CD8B1 gene Cell surface Cells Cessation of life Characteristics Chickens Complex Cross Presentation Cross-Priming Dendritic Cells Endoplasmic Reticulum Epitopes Funding Glycoproteins Goals Granulocyte-Macrophage Colony-Stimulating Factor Heat shock proteins Heating Histocompatibility Antigens Class I Home environment Homing Immune Infection Interferons Intravenous Invaded Lymphocytic choriomeningitis virus Lymphoid MHC Class I Genes Major Histocompatibility Complex Memory Modeling Molecular Mouse Pox Virus Mus Nucleoproteins Organ Orthopoxvirus Ovalbumin Ovum Pathogenesis Peptide/MHC Complex Peptides Population Proliferating Proteins Publishing Research Personnel Role Route SELL gene Secondary to Signal Transduction Spleen System T cell response T memory cell T-Cell Receptor T-Lymphocyte Testing Time Tissues Vaccinia virus Viral Viral Antigens Virus Virus Diseases Work beta-Galactosidase cell motility cell type experience flexibility flu in vivo influenzavirus intraperitoneal long term memory lymph nodes macrophage programs research study response secondary infection subcutaneous

项目摘要

We have previously shown that bone marrow-derived professional antigen presenting cells (pAPC) are essential to prime CD8+ T cell responses against several viruses. However, the cell types and mechanisms whereby these anti-viral responses are primed are still unsolved. The current model, mostly inferred from experiments with non-infectious antigens (Ags), proposes that dendritic cells carry Ags from infected tissues to secondary lymphoid organs (SLO) where CD8+ T cells are primed. We think that this model is too simplistic and cannot account for the priming of all anti-viral CD8+ T cell responses. Furthermore, this model does not address whether the pAPC in the infected tissues must become infected with the virus and migrate thereafter to directly prime the responses, or whether it must avoid its own infection and acquire the viral Ags from other infected cells in order to maintain its migratory capacity. In this case cross-presentation could be the major mechanism involved in priming. Another possibility is that pAPC may not need to transport viral Ags to SLO but become infected or acquire the viral Ags when they are already in the SLO. In this scenario, uninfected pAPC in the tissues could sense infection, and rapidly migrate to SLO to wait for the arrival of the virus. Our hypothesis is that, in order to minimize immune evasion, Ag presentation is a flexible system that could use any of these mechanisms in order to adapt to the type of invading virus and the route of infection. In this project we will test this hypothesis using VACV and LCMV as our model viruses with the following specific Aims: Specific Aim 1: To determine and compare the ability of macrophages and DC to migrate to secondary lymphoid organs during viral infections. Specific Aim 2: To determine the ability of macrophages and DC to prime and cross-prime anti-viral naive CD8+ T cells in vivo. Specific Aim 3: To determine the role of bone marrow-derived pAPC in the activation of memory CD8+ T cells. These experiments should provide important information to understand the pathogenesis of viral infections and the induction of anti-viral CD8+ T cell responses.

我们以前已经表明，骨髓来源的专业抗原呈递细胞（pAPC）是

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Memory CD8+ T cells are gatekeepers of the lymph node draining the site of viral infection.

记忆 CD8 T 细胞是病毒感染部位淋巴结引流的看门人。

DOI：
10.1073/pnas.0701822104
发表时间：
2007
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Xu,Ren-Huan;Fang,Min;Klein-Szanto,Andres;Sigal,LuisJ
通讯作者：
Sigal,LuisJ

Memory CD8⁺ T cells can outsource IFN-γ production but not cytolytic killing for antiviral protection.

记忆 CD8™ T 细胞可以外包 IFN-γ 的生产，但不能外包杀伤细胞以实现抗病毒保护。

DOI：
10.1016/j.chom.2013.04.004
发表时间：
2013
期刊：
Cell host & microbe
影响因子：
30.3
作者：
Remakus,Sanda;Rubio,Daniel;Lev,Avital;Ma,Xueying;Fang,Min;Xu,Ren-Huan;Sigal,LuisJ
通讯作者：
Sigal,LuisJ

CD94 is essential for NK cell-mediated resistance to a lethal viral disease.

DOI：
10.1016/j.immuni.2011.02.015
发表时间：
2011-04-22
期刊：
Immunity
影响因子：
32.4
作者：
Fang M;Orr MT;Spee P;Egebjerg T;Lanier LL;Sigal LJ
通讯作者：
Sigal LJ

Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection.

I 型干扰素表达和对急性 DNA 病毒感染的抵抗所需的两种病原体感应途径的顺序激活。

DOI：
10.1016/j.immuni.2015.11.015
发表时间：
2015-12-15
期刊：
Immunity
影响因子：
32.4
作者：
Xu RH;Wong EB;Rubio D;Roscoe F;Ma X;Nair S;Remakus S;Schwendener R;John S;Shlomchik M;Sigal LJ
通讯作者：
Sigal LJ

Direct presentation is sufficient for an efficient anti-viral CD8+ T cell response.