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人B7-1(CD80)和B7-2(CD86)与CD28和CTLA-4受体结合时亲和力相似,但动力学特性不同。

Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors.

作者信息

Linsley P S, Greene J L, Brady W, Bajorath J, Ledbetter J A, Peach R

机构信息

Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

出版信息

Immunity. 1994 Dec;1(9):793-801. doi: 10.1016/s1074-7613(94)80021-9.

Abstract

B7-0 or B7-2 (CD86) is a T cell costimulatory molecule that binds the same receptors (CD28 and CTLA-4) as B7-1 (CD80), but shares with it only approximately 25% sequence identity and is expressed earlier during an immune response. Here we show that human CD86 maintains similar (within approximately 2- to 3-fold) overall receptor binding and T cell costimulatory properties as CD80. However, CD80 and CD86 did not bind equivalently to CTLA-4: CD80 bound Y100A, a form of CTLA4lg with a mutation in the CDR3-like region, > 200-fold better than did CD86; inhibition of CD80-mediated cellular responses required approximately 100-fold lower CTLA4lg concentrations; and CD80-CTLA4lg complexes dissociated 5- to 8-fold more slowly, Thus, CD80 and CD86 utilize different binding determinants and have different kinetics of binding to CD28 and CTLA-4.

摘要

B7-0或B7-2(CD86)是一种T细胞共刺激分子,它与B7-1(CD80)结合相同的受体(CD28和CTLA-4),但与B7-1的序列同一性仅约为25%,且在免疫反应早期表达。我们在此表明,人CD86与CD80具有相似(约2至3倍范围内)的总体受体结合和T细胞共刺激特性。然而,CD80和CD86与CTLA-4的结合并不等同:CD80与Y100A(一种在类似CDR3区域有突变的CTLA4lg形式)的结合比CD86强200倍以上;抑制CD80介导的细胞反应所需的CTLA4lg浓度约低100倍;并且CD80-CTLA4lg复合物的解离速度慢5至8倍。因此,CD80和CD86利用不同的结合决定簇,并且与CD28和CTLA-4的结合动力学不同。

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