Malcherek G, Wirblich C, Willcox N, Rammensee H G, Trowsdale J, Melms A
Department of Neurology, University of Tübingen, Germany.
Eur J Immunol. 1998 May;28(5):1524-33. doi: 10.1002/(SICI)1521-4141(199805)28:05<1524::AID-IMMU1524>3.0.CO;2-T.
Proteolysis of the invariant chain (li) leads to the generation of abundant MHC class II-associated invariant chain peptides (CLIP), which bind in the MHC class II binding groove via supermotifs in a manner similar to that of antigenic peptides. We have engineered an li vector with the capacity to express any antigenic peptide of interest instead of CLIP, for T cell stimulation. When peripheral blood mononuclear cells (PBMC) were pulsed with li hybrids encoding T cell epitopes of tetanus toxin or acetylcholine receptor, stimulation of T cells was dramatically enhanced compared to stimulation after priming with either the native or recombinant proteins. Site-specific insertion of antigenic sequences into the CLIP region promoted enhanced antigenicity of li hybrids which were shown to be processed intracellularly in a chloroquine-sensitive compartment. Naturally processed T helper epitopes were visualized directly on the surface of PBMC and identified as analogs of CLIP associated with MHC class II molecules. This novel li vector provides a flexible and efficient system for the delivery of defined peptide epitopes to T cells which might be useful in the development of specific vaccines and in the study of intracellular processing.
恒定链（Ii）的蛋白水解作用导致大量MHC II类相关恒定链肽（CLIP）的产生，这些肽通过超基序以类似于抗原肽的方式结合在MHC II类结合槽中。我们构建了一种Ii载体，其能够表达任何感兴趣的抗原肽而非CLIP，用于T细胞刺激。当用编码破伤风毒素或乙酰胆碱受体T细胞表位的Ii杂种刺激外周血单个核细胞（PBMC）时，与用天然或重组蛋白致敏后的刺激相比，T细胞的刺激显著增强。将抗原序列位点特异性插入CLIP区域可促进Ii杂种抗原性增强，这些杂种在对氯喹敏感的区室中进行细胞内加工。天然加工的T辅助表位可直接在PBMC表面观察到，并被鉴定为与MHC II类分子相关的CLIP类似物。这种新型Ii载体为向T细胞递送特定肽表位提供了一个灵活而有效的系统，这可能在特定疫苗的开发和细胞内加工研究中有用。
