Jaraquemada D, Navarrete C, Ollier W, Awad J, Okoye R, Festenstein H
Hum Immunol. 1986 Jul;16(3):259-70. doi: 10.1016/0198-8859(86)90053-4.
Several lines of evidence indicate that HLA-Dw, as defined by HTC typing, is not the result of the combined stimulatory effect of HLA-DR and DQ. Therefore, responder cells do not have to share HLA-DQ antigens with the stimulator HTCs to give a typing response. The common HLA-DR-DQ associations observed in HTCs correspond to different patterns of linkage disequilibrium in different populations. HLA-DQ and HLA-Dw are functionally heterogeneous. Although HLA-DQ molecules may play a role in primary stimulation, this role is distinct from that of Dw determinants which have strong lymphocyte activating properties. The role of the HLA-DQ determinants on the other hand, is one of modulating the total T cell response by controlling the proliferation of suppressor and cytotoxic cells. The primary MLC response is the result of the proliferative effect of HLA-Dw, DR, DP, and other associated determinants, in conjunction with a modulatory effect of DQ molecules. However, HLA-Dw (as detected by HTC typing) are DR associated determinants which are immunodominant in primary MLR. The genes of the HLA-DR subregion have been named DR by the WHO nomenclature committee. This subregion encodes the HLA-DR specificities and the DRw52 and DRw53 determinants. Unfortunately this nomenclature does not take into account the need to define the genetic basis of the HLA-Dw determinants--whether they are encoded by separate genes within the HLA-DR subregion or whether they are encoded by as yet unspecified genes in the HLA class II region in linkage disequilibrium with HLA-DR DRw52/53. There are at least three and possibly four beta chain genes in the HLA-DR subregion, all in strong linkage disequilibrium with each other. Some of these are expressed in most haplotypes while others are not; some behave as pseudogenes in some haplotypes and in others, all the genes are expressed. All the genes of the class II region have not been fully characterized. HLA-Dw determinants may be specified by one or more of these genes. When more information becomes available, the genetic and molecular basis of the HLA-Dw series as well as the functional heterogeneity and antigenic strength of the various class II determinants will be better understood.
几条证据线索表明，通过混合淋巴细胞培养（HTC）分型所定义的HLA - Dw并非HLA - DR和DQ联合刺激作用的结果。因此，应答细胞不必与刺激HTC共享HLA - DQ抗原就能产生分型反应。在HTC中观察到的常见HLA - DR - DQ关联对应于不同人群中不同的连锁不平衡模式。HLA - DQ和HLA - Dw在功能上是异质的。虽然HLA - DQ分子可能在初次刺激中起作用，但该作用与具有强大淋巴细胞激活特性的Dw决定簇的作用不同。另一方面，HLA - DQ决定簇的作用是通过控制抑制性和细胞毒性细胞的增殖来调节总的T细胞反应。初次混合淋巴细胞培养（MLC）反应是HLA - Dw、DR、DP及其他相关决定簇的增殖作用与DQ分子的调节作用共同作用的结果。然而，HLA - Dw（通过HTC分型检测）是与DR相关联的决定簇，在初次混合淋巴细胞反应（MLR）中具有免疫显性。HLA - DR亚区的基因已由世界卫生组织命名委员会命名为DR。该亚区编码HLA - DR特异性以及DRw52和DRw53决定簇。不幸的是，这种命名法没有考虑到定义HLA - Dw决定簇的遗传基础的必要性——它们是由HLA - DR亚区内的单独基因编码，还是由与HLA - DR DRw52/53处于连锁不平衡状态的HLA II类区域中尚未明确指定的基因编码。HLA - DR亚区至少有三个且可能有四个β链基因，它们彼此之间都处于强连锁不平衡状态。其中一些在大多数单倍型中表达，而其他一些则不表达；一些在某些单倍型中表现为假基因，而在其他单倍型中，所有基因都表达。II类区域的所有基因尚未完全表征。HLA - Dw决定簇可能由这些基因中的一个或多个指定。当有更多信息可用时，HLA - Dw系列的遗传和分子基础以及各种II类决定簇的功能异质性和抗原强度将得到更好的理解。
