Kamikawaji N
Department of Genetics, Kyushu University, Fukuoka.
Fukuoka Igaku Zasshi. 1990 Feb;81(2):88-96.
Much attention has been paid whether there are any differences in regulating the human immune response between HLA-DR and -DQ molecules encoded by the genes within the HLA class II multigene family. Previous studies have suggested that HLA DQ molecules control low responsiveness through activating CD4 T cells which generate CD8 positive T cells, whereas HLA -DR molecules control high responsiveness through activating CD4 helper T cells. To examine this model we investigated the streptococcal cell wall antigen (SCW) specific T cell lines restricted by either DR or DQ molecule. To identify the restricting molecules, L cell transfectants expressing DQw1, DR2AB1 or DR2AB5 from Dw12 haplotype or DQw4, DR4 or DRw53 from DW15 haplotype were used. 1. From individuals with Dw12 which is a low responder haplotype to SCW, T cell clones specific to SCW and restricted by HLA-DQw1 or DR2 were identified, whereas from individuals with Dw15 which is a high responder haplotype, only DR4 or DRw53 restricted T cell clones were identified and DQw4 restricted T cells were never observed. 2. SCW specific CD4 T cells restricted by DQw1 were able to support the growth of CD8 positive cells, whereas those restricted by DR4 could not do so. 3. The CD8 T cells also required autologous antigen presenting cells and SCW to grow, and they completely blocked the immune response to SCW in vitro. These observations clearly demonstrated the distinct function of HLA-DQ and -DR molecules in regulating the human immune response to SCW.
人们一直非常关注在调节人类免疫反应方面，HLA Ⅱ类多基因家族内基因编码的 HLA -DR 和 -DQ 分子之间是否存在差异。先前的研究表明，HLA -DQ 分子通过激活产生 CD8 阳性 T 细胞的 CD4 T 细胞来控制低反应性，而 HLA -DR 分子通过激活 CD4 辅助性 T 细胞来控制高反应性。为了验证该模型，我们研究了受 DR 或 DQ 分子限制的链球菌细胞壁抗原（SCW）特异性 T 细胞系。为了鉴定限制分子，使用了从 Dw12 单倍型表达 DQw1、DR2AB1 或 DR2AB5 或从 DW15 单倍型表达 DQw4、DR4 或 DRw53 的 L 细胞转染体。1. 从对 SCW 呈低反应性单倍型的 Dw12 个体中，鉴定出了对 SCW 特异且受 HLA -DQw1 或 DR2 限制的 T 细胞克隆，而从对 SCW 呈高反应性单倍型的 Dw15 个体中，仅鉴定出了受 DR4 或 DRw53 限制的 T 细胞克隆，从未观察到受 DQw4 限制的 T 细胞。2. 受 DQw1 限制的 SCW 特异性 CD4 T 细胞能够支持 CD8 阳性细胞的生长，而受 DR4 限制的细胞则不能。3. CD8 T 细胞生长还需要自体抗原呈递细胞和 SCW，并且它们在体外完全阻断了对 SCW 的免疫反应。这些观察结果清楚地证明了 HLA -DQ 和 -DR 分子在调节人类对 SCW 的免疫反应中的不同功能。
