Hampl J, Gradehandt G, Plachov D, Gattner H G, Kalbacher H, Voelter W, Meyer-Delius M, Rüde E
Institut für Immunologie der Joh. Gutenberg Universität, Mainz, Germany.
Mol Immunol. 1991 Apr-May;28(4-5):479-87. doi: 10.1016/0161-5890(91)90162-d.
The requirements for insulin presentation and recognition by A alpha b A beta b- and A alpha b A beta k-restricted mouse T cells were studied using a variety of derivatives of the insulin A chain. It was found that A chain peptides with irreversibly blocked Cys residues are non-stimulatory for the T cells. This suggests that at least one of the Cys residues is essential for recognition. On the other hand, all A chain peptides containing Cys residues modified in a way reversible by reaction with thiols are stimulatory yet differ in antigenic potency. All these A chain derivatives including a 14 amino acid fragment require uptake by antigen presenting cells (APC) for efficient presentation. Differences in stimulatory potency between the A chain peptides derived from the same insulin appear to be mainly due to the efficiency of uptake and/or processing by APC. Based on these findings we propose that processing in the case of insulin and its A chain derivatives involves the reductive deblocking of Cys residues or the rearrangement of disulfide bonds apart from a possible proteolytic cleavage. The same may apply to other proteins if Cys residues in the presented peptides are important for the interaction with Ia or the T cell receptor.
利用胰岛素A链的多种衍生物，研究了AαbAβb和AαbAβk限制性小鼠T细胞对胰岛素呈递和识别的要求。发现具有不可逆阻断半胱氨酸残基的A链肽对T细胞无刺激作用。这表明至少有一个半胱氨酸残基对于识别至关重要。另一方面，所有含有可通过与硫醇反应可逆修饰的半胱氨酸残基的A链肽都具有刺激作用，但抗原效力不同。所有这些A链衍生物，包括一个14个氨基酸的片段，都需要抗原呈递细胞（APC）摄取才能有效呈递。源自同一胰岛素的A链肽之间刺激效力的差异似乎主要归因于APC摄取和/或加工的效率。基于这些发现，我们提出，胰岛素及其A链衍生物的加工过程除了可能的蛋白水解切割外，还涉及半胱氨酸残基的还原性去封闭或二硫键的重排。如果呈递肽中的半胱氨酸残基对于与Ia或T细胞受体的相互作用很重要，那么这可能也适用于其他蛋白质。
