Transfected Drosophila cells as a probe for defining the minimal requirements for stimulating unprimed CD8(+) T cells

被引:102
作者
Cai, ZL
Brunmark, A
Jackson, MR
Loh, D
Peterson, PA
Sprent, J
机构
[1] Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA
[2] RW JOHNSON PHARMACEUT RES INST, SAN DIEGO, CA 92121 USA
[3] NIPPON ROCHE RES CTR, KAMAKURA, KANAGAWA, JAPAN
关键词
D O I
10.1073/pnas.93.25.14736
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Stimulation of naive T cells by antigen-presenting cells (APC) is thought to involve two qualitatively different signals: signal one results from T-cell receptor (TCR) recognition of antigenic peptides bound to major histocompatibility complex (MHC) molecules, whereas signal two reflects contact with one or more costimulatory molecules, The requirements for stimulating naive T cells were studied with MHC class I-restricted CD8(+) T cells from a T-cell receptor transgenic line, with defined peptides as antigen and transfected Drosophila cells as APC. Three main findings are reported, First, stimulation of naive T cells via signal one alone (MHC plus peptide) was essentially nonimmunogenic; thus T cells cultured with peptides presented by MHC class I-transfected Drosophila APC lacking costimulatory molecules showed little or no change in their surface phenotype, Second, cotransfection of two costimulatory molecules, B7-1 and intercellular adhesion molecule 1 (ICAM-1), converted class I+ Drosophila cells to potent APC capable of inducing strong T-proliferative responses and cytokine (interleukin 2) production, Third, B7-1 and ICAM-1 acted synergistically, indicating that signal two is complex; synergy between B7-1 and ICAM-1 varied from moderate to extreme and was influenced by both the dose and affinity of the peptide used and the parameter of T-cell activation studied, Transfected Drosophila cells are thus a useful tool for examining the minimal APC requirements for naive T cells.
引用
收藏
页码:14736 / 14741
页数:6
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