Two distinct class II molecules encoded by the genes within HLA-DR subregion of HLA-Dw2 and Dw12 can act as stimulating and restriction molecules.
Two distinct class II molecules encoded by the genes within HLA-DR subregion of HLA-Dw2 and Dw12 can act as stimulating and restriction molecules.
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由 HLA-Dw2 和 Dw12 的 HLA-DR 亚区内的基因编码的两种不同的 II 类分子可以充当刺激分子和限制分子。
作者：
T. Sone;K. Tsukamoto;K. Hirayama;Y. Nishimura;T. Takenouchi;M. Aizawa;T. Sasazuki
通过二维聚丙烯酰胺凝胶电泳（2D-PAGE），我们研究了HLA- dw2和Dw12在HLA II类分子上的差异，两者血清学上都是HLA- dr2分型。抗hla - dr框架单克隆抗体（MoAb） HU-4从Dw2和Dw12纯合子B淋巴母细胞样细胞系中析出人II类分子的一条α链和两条β链。结果清楚地表明，Dw2和Dw12在2D-PAGE上的α链（α 1）和β链（β 1）的迁移率没有差异，但Dw2的另一个β链（β 2）在2D-PAGE上与Dw12不同。因此，MoAb HU-4从Dw2和Dw12中析出α 1 β 1和α 1 β 2分子，α 1 β 1分子可能是HLA-DR2分子。另一方面，α 1 β 2分子是II类分子，与抗dr2、抗dqw1 （DC1、MB1、MT1）或抗fa MoAbs沉淀的分子不同。MoAb HU-4完全抑制Dw2和Dw12之间的混合淋巴细胞培养反应（MLR），而抗dr2的MoAb HU-30仅与α 1 β 1分子反应，对Dw2和Dw12之间的混合淋巴细胞培养反应没有抑制作用。因此，α 1 β 2分子是引起Dw2和Dw12之间MLR的分子。对链球菌细胞壁抗原（SCW）有高反应的HLA-Dw12/D空白杂合子建立的IL - 2依赖性T细胞株清楚地区分了在抗原呈递细胞（APC）上表达的Dw2特异性和Dw12特异性。此外，MoAb HU-4显著抑制T细胞系与APC对SCW的合作反应。这些结果表明，α 1 β 2分子通过APC MoAb HU-30在SCW抗原呈递时被T细胞系识别为限制性分子，另一方面部分抑制了作为刺激细胞的Dw2或Dw12纯合细胞与作为应答细胞的非DR2细胞之间的MLR。明显抑制Dw2+但Dw12-异体APC表达的Dw12/D-杂合T细胞系对SCW的增殖反应，以及Dw2或Dw12纯合外周血淋巴细胞对SCW的外周反应。因此，由HLA-Dw2和Dw12的HLA-DR亚区基因编码的两种不同的II类分子可以在MLR中作为刺激分子，在APC抗原呈递中作为限制分子。
By using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), we investigated the difference in the HLA class II molecule between HLA-Dw2 and Dw12, both of which are typed as HLA-DR2 serologically. The anti-HLA-DR framework monoclonal antibody (MoAb) HU-4 precipitated an alpha-chain and two beta-chains of human class II molecules from both Dw2 and Dw12 homozygous B lymphoblastoid cell lines. It was demonstrated clearly that an alpha-chain (alpha 1) and one of the beta-chains (beta 1) showed no difference in mobility in the 2D-PAGE between Dw2 and Dw12, but that another beta chain (beta 2) of Dw2 was distinct from that of Dw12 in the 2D-PAGE profile. Thus, MoAb HU-4 precipitated alpha 1 beta 1 and alpha 1 beta 2 molecules from Dw2 and Dw12, and the alpha 1 beta 1 molecule appears to be an HLA-DR2 molecule. The alpha 1 beta 2 molecule, on the other hand, is a class II molecule distinct from those precipitated with anti-DR2, anti-DQw1 (DC1, MB1, MT1), or anti-FA MoAbs. MoAb HU-4 completely inhibited the mixed lymphocyte culture reaction (MLR) between Dw2 and Dw12, but anti-DR2 MoAb HU-30, which reacts only with the alpha 1 beta 1 molecule, did not show an inhibitory effect on the MLR between Dw2 and Dw12. The alpha 1 beta 2 molecule is therefore the molecule which elicits MLR between Dw2 and Dw12. An IL 2-dependent T cell line established from an HLA-Dw12/D blank heterozygous high responder to the streptococcal cell wall antigen (SCW) clearly distinguished the Dw2 specificity from Dw12 specificity expressed on the antigen-presenting cell (APC). Moreover, MoAb HU-4 markedly inhibited the cooperation between the T cell line and APC to respond to SCW. These observations indicate that the alpha 1 beta 2 molecule is recognized as a restriction molecule by the T cell line at the antigen presentation of SCW through APC MoAb HU-30 on the other hand partially inhibited the MLR between Dw2 or Dw12 homozygous cell as a stimulator cell and non DR2 cell as a responder cell. It markedly inhibited the proliferative response of the Dw12/D- heterozygous T cell line to SCW, presented by Dw2+ but Dw12- allogeneic APC, and the peripheral response of Dw2 or Dw12 homozygous peripheral blood lymphocytes to SCW. Thus, two distinct class II molecules encoded by the genes within the HLA-DR subregion of HLA-Dw2 and Dw12 can act as stimulating molecules in the MLR and as restriction molecules in the antigen presentation by APC.