Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
PLoS One. 2013;8(1):e51343. doi: 10.1371/journal.pone.0051343. Epub 2013 Jan 11.
Gamma-interferon-inducible lysosomal thiol reductase (GILT) is known to reduce disulfide bonds present in proteins internalized by antigen presenting cells, facilitating optimal processing and presentation of peptides on Major Histocompatibility Complex class II molecules, as well as the subsequent activation of CD4-positive T lymphocytes. Here, we show that GILT is required for class II-restricted processing and presentation of immunodominant epitopes from the major house dust mite allergen Der p 1. In the absence of GILT, CD4-positive T cell responses to Der p 1 are significantly reduced, resulting in mitigated allergic airway inflammation in response to Der p 1 and house dust mite extracts in a murine model of asthma.
γ-干扰素诱导的溶酶体硫醇还原酶(GILT)已知可还原抗原呈递细胞内内化蛋白中的二硫键,促进主要组织相容性复合体 II 类分子上肽的最佳加工和呈递,以及随后 CD4阳性 T 淋巴细胞的激活。在这里,我们表明 GILT 是主要尘螨过敏原 Der p 1 中免疫优势表位的 II 类限制加工和呈递所必需的。在缺乏 GILT 的情况下,对 Der p 1 的 CD4阳性 T 细胞反应显著降低,导致在哮喘小鼠模型中对 Der p 1 和尘螨提取物的过敏气道炎症减轻。