CYTOTOXIC T LYMPHOCYTE RESPONSE TO BACTERIAL INFECTION

细胞毒性 T 淋巴细胞对细菌感染的反应

• 批准号: 2442518
• 负责人: Eric G. Pamer
• 金额: $ 16.5万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2442518
• 关键词: Listeria; Listeria infections; MHC class I antigen; antigen presentation; bacterial proteins; cellular immunity; cytotoxic T lymphocyte; epitope mapping; immunoprecipitation; laboratory mouse; laboratory rabbit; protein purification; protein sequence; western blottings

Many pathogenic bacteria invade and multiply within cells. T lymphocytes are critical for an effective immune response to these intracellular pathogens. Infected cells process and present bacterial antigens to T lymphocytes using mechanisms that are interesting and incompletely understood. An excellent model of cellular immunity and bacterial antigen processing is the murine immune response to Listeria monocytogenes. CD8+ cytotoxic T lymphocytes (CTL) are important effectors of immunity to L. monocytogenes infection and recognize bacterial peptides presented by MHC class l molecules on the surface of infected cells. The peptide specificity of three CTL clones has recently been identified. LLO 91-99 derives from the secreted virulence factor listeriolysin and P6O 217-225 comes from the secreted P6O protein. Both are presented to CTL by the H- 2Kd MHC class l molecule. The third epitope, Fr38, is a secreted bacterial peptide that is presented to CTL by the H-2M3 non-classical MHC class l molecule. Preliminary studies show that these three epitopes appear in L. monocytogenes infected cells at different times and in markedly different quantities, and thus their relative contributions to the protective immune response may differ. The proposed studies will investigate the processing and presentation of the three L. monocytogenes CTL epitopes. The effect of cellular infection on MHC class l antigen processing and presentation will be determined. The possibility that the differences between these CTL epitopes may be of relevance to protective immunity will be explored. These studies will enhance our understanding of the CTL response to intracellular pathogens and may suggest new strategies for protection from intracellular pathogens. Additionally, these studies will increase our understanding of the interactions of pathogenic organisms with their mammalian hosts.

许多致病菌侵入细胞并在细胞内繁殖。 t淋巴细胞 对于针对这些细胞内 病原体被感染的细胞加工并将细菌抗原呈递给T 淋巴细胞使用的机制是有趣的， 明白 细胞免疫和细菌抗原的优良模型 处理是鼠对单核细胞增生李斯特菌的免疫应答。CD8 + 细胞毒性T淋巴细胞（CTL）是抗L. 单核细胞增多症感染和识别由MHC呈递的细菌肽 感染细胞表面的L类分子。 所述肽 最近鉴定了三种CTL克隆的特异性。LLO 91 - 99 来源于分泌的毒力因子β-溶血素和P6O 217 - 225 来自分泌的P6O蛋白。两者都是由H- 2Kd MHC I类分子。第三个表位Fr38是分泌的细菌表位， 由H-2M3非经典MHC I类呈递给CTL的肽 分子。 初步研究表明，这三个表位均存在于L。 单核细胞增多症感染细胞在不同的时间和在显着不同的 数量，因此它们对保护性免疫的相对贡献 答案可能不同。拟议的研究将调查处理 和三个L的介绍。单核细胞增多症CTL表位。 效果 细胞感染对MHC I类抗原加工和呈递的影响 将被确定。 这两种生物之间的差异 CTL表位可能与保护性免疫有关，将被探索。 这些研究将增强我们对CTL应答的理解， 细胞内的病原体，并可能提出新的战略， 胞内病原体 此外，这些研究将增加我们的 了解病原体与它们之间的相互作用 哺乳动物宿主

项目成果

MHC class I/peptide stability: implications for immunodominance, in vitro proliferation, and diversity of responding CTL.

MHC I 类/肽稳定性：对免疫优势、体外增殖和响应 CTL 多样性的影响。

• 发表时间: 1998
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Busch,DH;Pamer,EG
• 通讯作者: Pamer,EG

T cell affinity maturation by selective expansion during infection.

T细胞亲和力通过在感染过程中选择性扩张而成熟。

• DOI: 10.1084/jem.189.4.701
• 发表时间: 1999-02-15
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Busch, D H;Pamer, E G
• 通讯作者: Pamer, E G

CTL epitope generation is tightly linked to cellular proteolysis of a Listeria monocytogenes antigen.

CTL 表位的产生与单核细胞增生李斯特氏菌抗原的细胞蛋白水解密切相关。

• 发表时间: 1996
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Sijts,AJ;Villanueva,MS;Pamer,EG
• 通讯作者: Pamer,EG

Immunodominant and subdominant CTL responses to Listeria monocytogenes infection.

对单核细胞增生李斯特菌感染的免疫显性和亚显性 CTL 反应。

• 发表时间: 1997
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Vijh,S;Pamer,EG
• 通讯作者: Pamer,EG

Noncompetitive expansion of cytotoxic T lymphocytes specific for different antigens during bacterial infection.

在细菌感染期间，针对不同抗原的细胞毒性 T 淋巴细胞的非竞争性扩增。

• DOI: 10.1128/iai.67.3.1303-1309.1999
• 发表时间: 1999
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Vijh,S;Pilip,IM;Pamer,EG
• 通讯作者: Pamer,EG