Harris P E, Maffei A, Liu Z, Colovai I, Reed E F, Inghirami G, Suciu-Foca N
College of Physicians and Surgeons of Columbia University, Department of Pathology, New York, NY 10032.
J Immunol. 1993 Dec 1;151(11):5975-83.
Sequence analysis of HLA-class II (HLA-DR beta 1-1502 and 1104)-bound self-peptides from a transformed B cell line was performed. The sequences of naturally processed self-peptides bound to HLA-DR2 and DR5 were compared with protein and nucleic acid data bases for homology to known precursor proteins. Of the matches to known precursors, one peptide showed 100% homology to the third framework and CDR3 regions of Ig VH expressed by the line. Another peptide matched 100% to the human equivalent of macrophage inflammatory protein (MIP). A synthetic peptide corresponding to the naturally processed form of MIP (KPGVIFLTKRSRQV) was shown to inhibit Ag-specific HLA-DR beta 11104-restricted T cell proliferation. This indicates that the MIP peptide binds to HLA-DR beta 11104. The MIP peptide belongs to a set of peptides that showed uniform NH2-terminal processing. In this set, proline always occurred as the second residue followed by a basic lysine or arginine in position nine. This suggests that final NH2-terminal processing of peptides precedes their binding to MHC molecules. A distinct, second set of peptides showed ragged NH2-terminii, as has been reported for other naturally processed MHC-class II-bound self-peptides.
对来自一个转化的B细胞系的与HLA - II类分子（HLA - DRβ1 - 1502和1104）结合的自身肽段进行了序列分析。将与HLA - DR2和DR5结合的天然加工的自身肽段序列与蛋白质和核酸数据库进行比较，以寻找与已知前体蛋白的同源性。在与已知前体的匹配中，一个肽段与该细胞系表达的Ig VH的第三个构架区和CDR3区显示出100%的同源性。另一个肽段与人类巨噬细胞炎性蛋白（MIP）完全匹配。一个与天然加工形式的MIP（KPGVIFLTKRSRQV）相对应的合成肽段被证明可抑制抗原特异性的HLA - DRβ11104限制性T细胞增殖。这表明MIP肽段与HLA - DRβ11104结合。MIP肽段属于一组显示出一致的氨基末端加工的肽段。在这一组中，脯氨酸总是作为第二个残基出现，随后在第九位是碱性赖氨酸或精氨酸。这表明肽段的最终氨基末端加工先于它们与MHC分子的结合。另一组不同的肽段显示出参差不齐的氨基末端，正如其他天然加工的与MHC - II类分子结合的自身肽段所报道的那样。
