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一株抗原受体信号转导改变的T淋巴细胞体细胞突变体的分离与鉴定

Isolation and characterization of a T-lymphocyte somatic mutant with altered signal transduction by the antigen receptor.

作者信息

Goldsmith M A, Weiss A

机构信息

Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143.

出版信息

Proc Natl Acad Sci U S A. 1987 Oct;84(19):6879-83. doi: 10.1073/pnas.84.19.6879.

DOI:10.1073/pnas.84.19.6879
PMID:3309950
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC299188/
Abstract

We have developed an approach for deriving and characterizing antigen-receptor (CD3/Ti) signal-transduction mutants. This strategy combines receptor-mediated growth inhibition and fluorescence-activated cell sorting with the Ca2+-indicator indo-1. Despite the expression of structurally normal CD3/Ti complexes, one such mutant (J.CaM1) fails to exhibit inositolphospholipid metabolism or Ca2+ mobilization in response to anti-CD3 or anti-Ti monoclonal antibodies and fails to produce lymphokines in response to these antibodies. Surprisingly, anti-Ti antibody retains its effectiveness as a stimulus for the down-regulation of CD3/Ti surface expression. These cells remain responsive to AIF-4, at least one anti-CD3 antibody, and some combinations of nonagonist anti-Ti and anti-CD3 antibodies. The mutation in J.CaM1 appears to lie in a proximal component of the signal-transduction apparatus.

摘要

我们已开发出一种用于推导和表征抗原受体（CD3/Ti）信号转导突变体的方法。该策略将受体介导的生长抑制、荧光激活细胞分选与Ca2+指示剂indo-1相结合。尽管表达了结构正常的CD3/Ti复合物，但其中一个这样的突变体（J.CaM1）在响应抗CD3或抗Ti单克隆抗体时，未能表现出肌醇磷脂代谢或Ca2+动员，并且在响应这些抗体时未能产生淋巴因子。令人惊讶的是，抗Ti抗体作为CD3/Ti表面表达下调的刺激物仍保持其有效性。这些细胞对AIF-4、至少一种抗CD3抗体以及非激动剂抗Ti和抗CD3抗体的某些组合仍有反应。J.CaM1中的突变似乎位于信号转导装置的近端组件中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65cf/299188/9f5df3d4a228/pnas00334-0278-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65cf/299188/538194415a97/pnas00334-0278-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65cf/299188/9f5df3d4a228/pnas00334-0278-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65cf/299188/538194415a97/pnas00334-0278-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65cf/299188/9f5df3d4a228/pnas00334-0278-b.jpg

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