MAJOR HISTOCOMPATIBILITY COMPLEX BINDING-AFFINITY OF AN ANTIGENIC DETERMINANT IS CRUCIAL FOR THE DIFFERENTIAL SECRETION OF INTERLEUKIN-4/5 OR INTERFERON-GAMMA BY T-CELLS
MAJOR HISTOCOMPATIBILITY COMPLEX BINDING-AFFINITY OF AN ANTIGENIC DETERMINANT IS CRUCIAL FOR THE DIFFERENTIAL SECRETION OF INTERLEUKIN-4/5 OR INTERFERON-GAMMA BY T-CELLS
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DOI：
10.1073/pnas.92.21.9510
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发表时间：
1995-10-10
影响因子：
11.1
通讯作者：
SERCARZ, E
中科院分区：
文献类型：
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作者：
KUMAR, V;BHARDWAJ, V;SERCARZ, E
体内CD4(+)T细胞前体的不同激活导致了具有独特淋巴因子分泌模式的效应器的发展。为了研究淋巴因子分泌的差异模式是否受到与配体的显示和/或识别相关的因素的影响，我们使用了一组具有不同II类结合亲和力但T细胞特异性不变的配体。与I-A(U)结合约10,000倍的配体显著增加了体内分泌干扰素伽马的细胞的频率，但不能增加分泌IL-4或IL-5的细胞的频率。使用已建立的仅分泌IL-4的配体特异性的CD4(+)T细胞克隆，我们还证明了在体外，亲和力最高的配体刺激会导致干扰素伽马的产生。相反，表现出相对较低的II类结合的配体只能诱导IL-4的分泌。这些数据表明，抗原决定簇的主要组织相容性复合体结合亲和力，导致T细胞-抗原呈递细胞界面上的不同相互作用，可能对T细胞中细胞因子模式的不同发展至关重要。
Differential activation of CD4(+) T-cell precursors in vivo leads to the development of effecters with unique patterns of lymphokine secretion. To investigate whether the differential pattern of lymphokine secretion is influenced by factors associated with either the display and/or recognition of the ligand, we have used a set of ligands with various class II binding affinities but unchanged T-cell specificity. The ligand that exhibited approximate to 10,000-fold higher binding to I-A(u) considerably increased the frequency of interferon gamma-producing but not interleukin (IL) 4- or IL-5-secreting cells in vivo. Using an established ligand-specific, CD4(+) T-cell clone secreting only IL-4, we also demonstrated that stimulation with the highest affinity ligand resulted in interferon gamma production in vitro. In contrast, ligands that demonstrated relatively lower class II binding induced only IL-4 secretion. These data suggest that the major histocompatibility complex binding affinity of antigenic determinants, leading to differential interactions at the T cell-antigen-presenting cell interface, can be crucial for the differential development of cytokine patterns in T cells.