Donermeyer D L, Allen P M
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1989 Feb 15;142(4):1063-8.
A 34 amino acid hen egg-white lysozyme (HEL) peptide was designed and synthesized to investigate if an immunogenic peptide once bound to an Ia molecule becomes proteolytically inaccessible. The determinant recognized by T cells, HEL(52-61) was composed of L-amino acids whereas the 12 amino acid extension on each side of this core were composed of D-epimers. This peptide, HEL(40-73) was resistant to proteolysis, except in the core region, where any cleavage would destroy the determinant. Initially HEL(40-73) was shown to be able to stimulate the HEL specific T cell, 3A9, indicating that an I-Ak molecule can bind and present large peptides that extend beyond the theoretical binding groove. HEL(40-73) was then used to examine the proteolytic sensitivity of determinants recognized by T cells. If HEL(40-73) was treated with chymotrypsin before binding to I-Ak, the determinant was totally destroyed; however, if HEL(40-73) was allowed to first bind to I-Ak, then the determinant became resistant to chymotrypsin cleavage. Thus an Ia molecule can protect a determinant from proteolytic degradation, a finding that has important implications for proposed pathways of Ag processing.
设计并合成了一种34个氨基酸的鸡蛋清溶菌酶（HEL）肽，以研究一旦与Ia分子结合的免疫原性肽是否会变得对蛋白水解具有抗性。T细胞识别的决定簇HEL(52 - 61)由L - 氨基酸组成，而该核心两侧的12个氨基酸延伸部分由D - 表位组成。这种肽HEL(40 - 73)除核心区域外对蛋白水解具有抗性，在核心区域任何切割都会破坏决定簇。最初，HEL(40 - 73)被证明能够刺激HEL特异性T细胞3A9，这表明I - Ak分子可以结合并呈递超出理论结合槽的大肽。然后使用HEL(40 - 73)来检测T细胞识别的决定簇的蛋白水解敏感性。如果在与I - Ak结合之前用胰凝乳蛋白酶处理HEL(40 - 73)，决定簇会被完全破坏；然而，如果先让HEL( + 73)与I - Ak结合，那么决定簇就会对胰凝乳蛋白酶切割产生抗性。因此，Ia分子可以保护决定簇免受蛋白水解降解，这一发现对提出的抗原加工途径具有重要意义。
