Lorenz R G, Tyler A N, Allen P M
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1988 Dec 15;141(12):4124-8.
Bovine RNase A specific T-cell hybridomas were generated to study the recognition of foreign Ag by T lymphocytes. One hybrid, TS12, was shown to recognize RNase in association with I-Ak. This hybridoma required bovine RNase to be processed before recognition. The immunogenic determinant on the RNase molecule recognized by TS12 was localized to the tryptic fragment RNase(40-61). All of the stimulatory ability of this determinant was shown to be contained within the synthetic 14mer RNase(43-56). When this segment of bovine RNase was compared with the self murine sequence, only one amino acid difference was found, a substitution of a proline residue at position 50 for a serine residue. This substitution completely abolishes binding to the I-Ak molecule, as shown by both functional and direct binding assays. This finding shows that self/non-self discrimination not only occurs at the level of the T cell, but also can be caused by an inability of the self peptide to associate with a class II molecule.
为了研究T淋巴细胞对外源抗原的识别，制备了牛核糖核酸酶A特异性T细胞杂交瘤。其中一个杂交瘤TS12被证明可识别与I-Ak相关的核糖核酸酶。该杂交瘤在识别前需要对牛核糖核酸酶进行加工处理。TS12识别的核糖核酸酶分子上的免疫原性决定簇定位于胰蛋白酶片段核糖核酸酶(40 - 61)。该决定簇的所有刺激能力都存在于合成的14聚体核糖核酸酶(43 - 56)中。当将牛核糖核酸酶的这一片段与自身小鼠序列进行比较时，仅发现一个氨基酸差异，即第50位的脯氨酸残基被丝氨酸残基取代。如功能和直接结合试验所示，这种取代完全消除了与I-Ak分子的结合。这一发现表明，自身/非自身的区分不仅发生在T细胞水平，也可能是由于自身肽无法与II类分子结合所致。
