Nikcevich K M, Kopielski D, Finnegan A
Department of Immunology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Cell Immunol. 1996 Sep 15;172(2):254-61. doi: 10.1006/cimm.1996.0240.
Several published reports have lead to the characterization of naturally processed peptides that are presented in association with either class I or class II MHC molecules. Most peptides isolated from class II molecules are heterogeneous in length and exhibit ragged amino and carboxy termini. An intriguing finding was that one region of a molecule was often represented by many distinct peptides, rather than by a single dominant peptide species. Each of the peptides representing this dominant region exhibited a common core of amino acids, suggesting that this core may play a significant role in the binding of the peptide to class II and the recognition by peptide-specific T cells. Work from our laboratory has focused on the mechanisms involved in the immunodominance of antigenic determinants using the bacterial antigen Staphylococcal nuclease (Nase) as a model. Using truncated synthetic peptides, we have identified the immunodominant determinant of Nase to be located within the region 81-100 with a minimal antigenic core of 91-100 as determined. Addition of five residues to the carboxy terminus of this peptide had a negative effect on T cell recognition of this region. The present studies were undertaken in an effort to determine the sequence of the naturally processed immunodominant Nase determinant(s) presented in association with I-Ek class II. Our results indicate that the dominant region of the Nase molecule is represented by at least four distinct peptide species that are predicted to lie between residues 86 and 106 with a common core sequence of 91-96. These results indicate that the negative effects of flanking regions are dependent upon length and amino acid composition, and thus the use of truncated peptides to study minimal antigenic determinants may be misleading.
几篇已发表的报告对与I类或II类MHC分子相关呈递的天然加工肽进行了表征。从II类分子中分离出的大多数肽长度各异，且氨基端和羧基端参差不齐。一个有趣的发现是，分子的一个区域通常由许多不同的肽代表，而不是由单一的优势肽种类代表。代表这个优势区域的每一种肽都表现出一个共同的氨基酸核心，这表明这个核心可能在肽与II类分子的结合以及肽特异性T细胞的识别中发挥重要作用。我们实验室的工作一直聚焦于以细菌抗原葡萄球菌核酸酶（Nase）为模型，研究抗原决定簇免疫显性所涉及的机制。使用截短的合成肽，我们已确定Nase的免疫显性决定簇位于81 - 100区域内，确定其最小抗原核心为91 - 100。在该肽的羧基端添加五个残基对该区域的T细胞识别有负面影响。进行本研究是为了确定与I - Ek II类分子相关呈递的天然加工免疫显性Nase决定簇的序列。我们的结果表明，Nase分子的优势区域由至少四种不同的肽种类代表，预计这些肽位于86至106位残基之间，共同核心序列为91 - 96。这些结果表明侧翼区域的负面影响取决于长度和氨基酸组成，因此使用截短肽来研究最小抗原决定簇可能会产生误导。
