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NATURAL HIV-1 PEPTIDES AND CD8+ CYTOTOXIC T-CELLS

天然 HIV-1 肽和 CD8 细胞毒性 T 细胞

基本信息

批准号：
2442546
负责人：
HERMAN N EISEN
金额：
$ 27.15万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-07-01 至 1998-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2442546
关键词：
CD8 molecule HIV infections MHC class I antigen cellular immunity chemical binding cytotoxic T lymphocyte human immunodeficiency virus 1 immunoaffinity chromatography leukocyte activation /transformation mass spectrometry protein sequence tissue /cell culture virus protein

项目摘要

By destroying virus-infected cells, CD8+ cytotoxic T lymphocytes (CTL) contribute to the termination of viral infections and play an important role in immune defenses against many viruses. Although CTL are found in substantial numbers in individuals infected with human immunodeficiency virus type 1 (HIV-1) and may help lower the viral burden in these individuals, these cells do not succeed in eliminating HIV-1 infection. To help understand why these cells are not more effective in HIV-1 infections and to help lay the groundwork for a more rational development of vaccines aimed at enhancing the production and effectiveness of these cells, we will identify and analyze the naturally occurring peptides of HIV-1 origin in HIV-1 infected cells. The peptides analyzed will be principally those that are recognized in association with class I MHC class proteins by CD8+ CTL clones or lines from HIV-1 infected individuals. We will also analyze the most abundant HIV-1 peptides associated with class I MHC proteins from infected cells. All of these peptides will be characterized in terms of their a) amino acid sequence, b) abundance as adducts of class I MHC proteins isolated from cells that are producing HIV-1, and c) their affinity (intrinsic equilibrium association constant) for MHC-I proteins. To achieve these goals we will use specially constructed stable, cultured cell lines in which every cell produces HIV virus and expresses a class I MHC protein chosen to represent one of the more common ones in human populations and that restrict recognition of HIV-1 peptides by human cytotoxic T cell clones. These specially constructed HIV-1 producing cell lines and antigen-processing mutant cells (such as T2) that can be loaded exogenously with synthetic peptides will be used as stimulator cells to elicit new CD8+ CTL cell lines and clones from HIV-1 infected individuals of appropriate HLA type (e.g. HLA-H2); the cytolytic effectiveness of the new clones will be evaluated and the peptides they recognize (in association with MHC-1) will also be analyzed as described.

通过破坏病毒感染的细胞，CD 8+细胞毒性T淋巴细胞（CTL）有助于终止病毒感染，在抵抗许多病毒的免疫防御中起重要作用。虽然CTL 在人类感染的个体中发现了大量的免疫缺陷病毒1型（HIV-1），并可能有助于降低病毒在这些人的负担，这些细胞不能成功地消除 HIV-1感染。为了帮助理解为什么这些细胞有效的HIV-1感染，并帮助奠定基础，更合理地开发疫苗，生产和这些细胞的有效性，我们将确定和分析HIV-1中HIV-1来源的天然肽被感染的细胞分析的肽将主要是那些与I类MHC类蛋白结合被CD 8 + 来自HIV-1感染个体的CTL克隆或系。我们还将分析与I类MHC相关的最丰富的HIV-1肽感染细胞的蛋白质。所有这些肽将被根据它们的a）氨基酸序列，B）丰度作为I类MHC蛋白的加合物，所述I类MHC蛋白分离自产生HIV-1，和c）它们的亲和力（内在平衡结合常数）。为了实现这些目标，我们将使用特别构建的稳定的培养细胞系，每个细胞都能产生HIV病毒并表达I类MHC蛋白选择代表人类中最常见的一种并限制人细胞毒性T细胞对HIV-1肽的识别细胞克隆这些特别构建的HIV-1生产细胞系和抗原加工突变细胞（如T2），外源性合成肽将被用作刺激细胞从HIV-1感染者中诱导新的CD 8 + CTL细胞系和克隆，合适HLA类型（例如HLA-H2）的个体;细胞溶解性将评估新克隆的有效性，它们识别的（与MHC-1相关）也将被分析为介绍了

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Variations in the number of peptide-MHC class I complexes required to activate cytotoxic T cell responses.

激活细胞毒性 T 细胞反应所需的肽-MHC I 类复合物数量的变化。

DOI：
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Kageyama,S;Tsomides,TJ;Sykulev,Y;Eisen,HN
通讯作者：
Eisen,HN

Anti-melanoma cytotoxic T lymphocytes (CTL) recognize numerous antigenic peptides having 'self' sequences: autoimmune nature of the anti-melanoma CTL response.

抗黑色素瘤细胞毒性 T 淋巴细胞 (CTL) 识别许多具有“自身”序列的抗原肽：抗黑色素瘤 CTL 反应的自身免疫性质。

DOI：
10.1093/intimm/9.2.327
发表时间：
1997
期刊：
International immunology
影响因子：
4.4
作者：
Tsomides,TJ;Reilly,EB;Eisen,HN
通讯作者：
Eisen,HN

Increased generation of CD8+ T cell clones in p53 mutant mice.

p53 突变小鼠中 CD8 T 细胞克隆的产生增加。

DOI：
发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Zhou,X;Wong,S;Walter,J;Jacks,T;Eisen,HN
通讯作者：
Eisen,HN

Stimulation of human cytotoxic T cells with HIV-1-derived peptides presented by recombinant HLA-A2 peptide complexes.

用重组 HLA-A2 肽复合物呈递的 HIV-1 衍生肽刺激人细胞毒性 T 细胞。

DOI：
10.1093/intimm/9.3.451
发表时间：
1997
期刊：
International immunology
影响因子：
4.4
作者：
Walter,JB;Brander,C;Mammen,M;Garboczi,DN;Kalams,SA;Whitesides,GM;Walker,BD;Eisen,HN
通讯作者：
Eisen,HN

Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells chronically infected by human immunodeficiency virus type 1.