Ottenhoff T H, Walford C, Nishimura Y, Reddy N B, Sasazuki T
Armauer Hansen Research Institute, Kyushu University, Fukuoka.
Eur J Immunol. 1990 Oct;20(10):2347-50. doi: 10.1002/eji.1830201027.
The major histocompatibility complex (MHC) controls of the outcome of the immune response to T cell-dependent antigens by dictating whether T cell responsiveness will result (MHC-immune response [Ir]genes) or alternatively T cell nonresponsiveness will occur, possibly through the activation of suppressor cells (MHC-immune suppression [Is] genes). In mice, I-A molecules typically restrict antigen-specific helper T cells. In contrast, H-2 I-E molecules have been reported to control nonresponsiveness to a variety of antigens through antigen-specific suppressor cells. In analogy, HLA-DR molecules are the dominant restriction elements for helper T cells in man. This forces the question whether DQ molecules may be involved in controlling nonresponsiveness in man, e.g. through suppression. In one system, T cell nonresponsiveness to Schistosoma japonicum, evidence has been presented supporting this notion. We have now used a second system, Mycobacterium leprae-specific T cell nonresponsiveness, that is typically found in lepromatous leprosy patients. We find positive but limited evidence for a role for HLA-DQ molecules in controlling T cell nonresponsiveness to M. leprae of the 22 nonresponder patients tested, 4 showed a proliferative T cell response to M. leprae after the addition of DQ- but not DR-specific mAb to the cell cultures. In one of the four BCG nonresponders, anti-DQ mAb had a similar effect.
主要组织相容性复合体（MHC）通过决定T细胞反应性是否会产生（MHC免疫反应[Ir]基因）来控制对T细胞依赖性抗原的免疫反应结果，或者相反，T细胞无反应性是否会发生，这可能是通过抑制细胞的激活（MHC免疫抑制[Is]基因）。在小鼠中，I-A分子通常限制抗原特异性辅助性T细胞。相比之下，据报道H-2 I-E分子通过抗原特异性抑制细胞来控制对多种抗原的无反应性。类似地，HLA-DR分子是人类辅助性T细胞的主要限制元件。这就引发了一个问题，即DQ分子是否可能参与控制人类的无反应性，例如通过抑制作用。在一个系统中，针对日本血吸虫的T细胞无反应性，已经有证据支持这一观点。我们现在使用了第二个系统，即麻风分枝杆菌特异性T细胞无反应性，这在瘤型麻风患者中很常见。我们发现，对于HLA-DQ分子在控制对麻风分枝杆菌的T细胞无反应性方面的作用，有一些正面但有限的证据。在所测试的22名无反应患者中，4名患者在细胞培养物中加入DQ特异性单克隆抗体（而不是DR特异性单克隆抗体）后，对麻风分枝杆菌出现了增殖性T细胞反应。在4名卡介苗无反应者中的1名中，抗DQ单克隆抗体也有类似的效果。
