Stevanović Stefan, Lemmel Claudia, Häntschel Maik, Eberle Ute
Eberhard-Karls-Universität Tübingen, Institut für Zellbiologie, Abteilung Immunologie, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.
Novartis Found Symp. 2003;254:143-55; discussion 155-64, 216-22, 250-2.
During the past few years, a huge amount of information about HLA-presented peptides has been compiled: several thousand naturally processed ligands of such cell surface receptors are already known. Nevertheless, our knowledge covers only a minute proportion of the total peptide repertoire. The overall amount of different peptides presented by one given HLA class I molecule lies between 1000 and 10000 individual sequences per cell. There is, however, no HLA molecule of which more than 100 ligands have been published so far. The situation is further complicated by the fact that different cells present different sets of peptides by the same HLA molecules, a feature that provides great hope for immunotherapy. We have been analysing HLA-presented peptides for many years for three reasons. First, the basic rules of peptide presentation (the 'peptide motifs') had to be established. Second, the listing of individual peptides presented by HLA molecules is steadily continuing, although a comprehensive catalogue of all possible HLA-presented peptides is utopical in our days. Third, quantitative differences in the presentation of individual HLA ligands provide information about the dynamic state of the host cells. Comprehensive information about HLA-presented peptides enables accurate epitope prediction and provides a basis for diagnostic assessment and therapeutic intervention.
在过去几年中,已经汇编了大量关于HLA呈递肽的信息:已知数千种此类细胞表面受体的天然加工配体。然而,我们的知识仅涵盖总肽库的极小一部分。单个给定的HLA I类分子呈递的不同肽的总量在每个细胞1000至10000个单独序列之间。然而,迄今为止,尚未有超过100种配体的HLA分子被公布。同一HLA分子在不同细胞中呈递不同的肽组,这一事实使情况更加复杂,这一特征为免疫治疗带来了巨大希望。多年来,我们一直在分析HLA呈递的肽,原因有三个。首先,必须确立肽呈递的基本规则(“肽基序”)。其次,HLA分子呈递的单个肽的列表仍在不断更新,尽管在当今时代编制所有可能的HLA呈递肽的综合目录是不切实际的。第三,单个HLA配体呈递的数量差异提供了有关宿主细胞动态状态的信息。关于HLA呈递肽的全面信息能够实现准确的表位预测,并为诊断评估和治疗干预提供依据。