Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, United States of America.
PLoS One. 2010 May 12;5(5):e10599. doi: 10.1371/journal.pone.0010599.
Gamma interferon Inducible Lysosomal Thiol reductase (GILT) is a unique lysosomal reductase that reduces disulfide bonds of endocytosed proteins. Lack of GILT clearly decreases CD4 T cell-antigen specific responses against some epitopes of antigens containing disulfide bonds, but not to proteins with few or no disulfide bridges. Hence, global impact of GILT on antigen presentation is currently not well understood. We used Nano-LC-ESI-MS/MS to investigate how GILT affects diversity of self-peptides presented by MHC class II molecules. Surprisingly, the repertoire of self-peptides in the absence of GILT does not appear to be significantly different, as only few peptide species (approximately 2%) were found to be the unique indicators of GILT's presence or absence. In the absence of GILT about thirty peptide species (approximately 5%) were found either uniquely or fourteen to hundred fold more abundantly expressed than in the presence of GILT. Our data indicate that GILT has limited yet unexpected effect on self-peptide species presented by MHC class II antigens.
γ干扰素诱导溶酶体硫醇还原酶（GILT）是一种独特的溶酶体还原酶，可还原内吞蛋白的二硫键。缺乏 GILT 明显会降低 CD4 T 细胞针对某些含有二硫键的抗原表位的抗原特异性反应，但不会降低含有少量或没有二硫键的蛋白质的反应。因此，目前尚不清楚 GILT 对抗原呈递的全面影响。我们使用纳升液相色谱-电喷雾串联质谱（Nano-LC-ESI-MS/MS）来研究 GILT 如何影响 MHC Ⅱ类分子呈递的自身肽的多样性。令人惊讶的是，缺乏 GILT 时自身肽的库似乎没有明显不同，因为只有少数肽种类（约 2%）被发现是 GILT 存在或不存在的独特标志物。在缺乏 GILT 的情况下，大约有三十种肽种类（约 5%）的表达要么是独特的，要么是在有 GILT 的情况下表达增加了十四到一百倍。我们的数据表明，GILT 对 MHC Ⅱ类抗原呈递的自身肽种类的影响有限，但出乎意料。
