Lovitch Scott B, Petzold Shirley J, Unanue Emil R
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
J Immunol. 2003 Sep 1;171(5):2183-6. doi: 10.4049/jimmunol.171.5.2183.
We quantitated the amounts of peptides from hen egg-white lysozyme presented by I-A(k) molecules in APC lines. The large chemical gradient of presentation of the four hen egg-white lysozyme epitopes observed in cell lines expressing HLA-DM or H-2DM (referred to in this study as DM) was significantly diminished in the T2.A(k) line lacking DM. Differences in levels of presentation between wild-type and DM-deficient APC were observed for all four epitopes, but differences were most evident for the highest affinity epitope. As a result of these quantitative differences in display, presentation of all four epitopes to T cells was impaired in the line lacking DM. The binding affinity of the pool of naturally processed peptides from DM-expressing lines was higher than that from the DM-deficient line. Thus, using a direct biochemical approach in APC, we demonstrate that DM influences the selection of peptides bound to MHC class II by favoring high affinity peptides.
我们对抗原呈递细胞（APC）系中由I-A(k)分子呈递的来自鸡蛋清溶菌酶的肽量进行了定量。在表达HLA-DM或H-2DM（本研究中称为DM）的细胞系中观察到的四种鸡蛋清溶菌酶表位呈递的大化学梯度，在缺乏DM的T2.A(k)细胞系中显著减小。对于所有四种表位，均观察到野生型和缺乏DM的APC之间呈递水平的差异，但对于亲和力最高的表位，差异最为明显。由于这些呈递中的定量差异，在缺乏DM的细胞系中，所有四种表位向T细胞的呈递均受损。来自表达DM的细胞系的天然加工肽库的结合亲和力高于来自缺乏DM的细胞系的。因此，通过在APC中使用直接生化方法，我们证明DM通过偏向高亲和力肽来影响与MHC II类结合的肽的选择。
