Williams D B, Ferguson J, Gariepy J, McKay D, Teng Y T, Iwasaki S, Hozumi N
Samuel Lunenfeld Research Institute Mount Sinai Hospital, Department of Immunology, University of Toronto, Ontario, Canada.
J Immunol. 1993 Oct 1;151(7):3627-37.
Data are presented which demonstrate the minimal insulin peptide required to activate a large group of insulin-specific T hybrids following presentation by either live or fixed APC, is the N-terminal insulin-A(1-13) peptide. Functional activation and competition assays using both live and fixed APC with 19 synthesized variants of the N-terminal bovine insulin A-chain molecule permitted classification of peptide residues into MHC agretope and T cell epitope regions. Our findings indicate insulin A-chain peptide occupies the Ag binding groove of class II MHC in an extended conformation as a result of intracellular reduction of A-loop disulfide bonds. Insulin A-chain Cys7 and Cys11 residues represent two independent T cell epitopes N- and C-terminal to the A-loop region. Data are presented that demonstrate the unique residues associated with several insulin isoform molecules contribute to the peptide agretope region. Our findings may suggest peptide agretopes may subtly modify the peptide/MHC conformation presented to TCR.
所呈现的数据表明，在由活的或固定的抗原呈递细胞（APC）呈递后，激活大量胰岛素特异性T杂交细胞所需的最小胰岛素肽是N端胰岛素-A(1-13)肽。使用活的和固定的APC以及N端牛胰岛素A链分子的19种合成变体进行的功能激活和竞争试验，使得能够将肽残基分类为MHC抗原结合基序和T细胞表位区域。我们的研究结果表明，由于A环二硫键的细胞内还原，胰岛素A链肽以伸展构象占据II类MHC的抗原结合槽。胰岛素A链的Cys7和Cys11残基代表A环区域N端和C端的两个独立T细胞表位。所呈现的数据表明，与几种胰岛素同工型分子相关的独特残基有助于肽抗原结合基序区域。我们的研究结果可能表明，肽抗原结合基序可能会微妙地改变呈递给TCR的肽/MHC构象。
