Chou K Y, Fu S L, Li N L, Huang L D, Wang F Q, Lu P H, Fan L A
Shanghai Institute of Immunology, Shanghai Second Medical University, China.
Eur J Immunogenet. 1999 Feb;26(1):5-13. doi: 10.1046/j.1365-2370.1999.00124.x.
The initiation of a CD8 cell-mediated pathway (M+) was adopted as a phenotypic trait to analyse genetic predisposition in trichosanthin (Tk)-induced immuno-suppression. Tk is a natural protein antigen with 247 amino acid residues. Based on DNA typing for DR, DQ, DP and TAP genes, data in this paper indicate that only DQ genes were primarily involved and that the alleles DQA10501 and DQB10201 were strongly associated with the M+ phenotype in cis (on DR3 haplotype) or trans (on DR5/DR7 heterozygotes) complementation. This is consistent with our observation that only the DQ-positive cells were capable of expanding after being co-cultured with Tk for 96 h. Two points of interest were noted. (1) The susceptible haplotype DRB10301-DQA10501-DQB10201 showed an association with the M+ phenotype only if combined with DRB104-, DRB108-, or DRB109-related haplotypes. When co-presented with DRB111-, DRB115-, DRB107-related haplotypes, however, no cis complementation could be detected. A detailed analysis of the association patterns indicated that the DQB1 locus of the non-susceptible haplotypes was the main factor for up- or down-modulation. (2) For M+ phenotype-related trans complementation in Tk-induced suppression, it was found that not only DQA10501-DQB10201 (DR5/7) alleles, but also associated DQA10301-DQB10201 (DR4/7, 9/7) alleles, were involved. The allele DQB10201 was not associated with the DQA1 alleles in DRB101-, DRB115-, DRB113-, DRB107-related haplotypes. The results obtained indicate that there are some additional genetic factors involved in the functional expression of cis and trans complementation of DQA1 and DQB1 genes, among which the DQ alleles play a critical role as self-regulators.
采用CD8细胞介导途径（M+）的启动作为一种表型特征，来分析天花粉蛋白（Tk）诱导的免疫抑制中的遗传易感性。Tk是一种具有247个氨基酸残基的天然蛋白质抗原。基于DR、DQ、DP和TAP基因的DNA分型，本文数据表明，主要只有DQ基因参与其中，并且等位基因DQA10501和DQB10201在顺式（在DR3单倍型上）或反式（在DR5/DR7杂合子上）互补中与M+表型强烈相关。这与我们的观察结果一致，即只有DQ阳性细胞在与Tk共培养96小时后能够扩增。注意到两点。（1）易感单倍型DRB10301-DQA10501-DQB10201仅在与DRB104-、DRB108-或DRB109相关单倍型组合时才与M+表型相关。然而，当与DRB111-、DRB115-、DRB107相关单倍型同时出现时，无法检测到顺式互补。对关联模式的详细分析表明，非易感单倍型的DQB1基因座是上调或下调的主要因素。（2）对于Tk诱导的抑制中与M+表型相关的反式互补，发现不仅DQA10501-DQB10201（DR5/7）等位基因，而且相关的DQA10301-DQB10201（DR4/7、9/7）等位基因也参与其中。等位基因DQB10201在DRB101-、DRB115-、DRB113-、DRB107相关单倍型中与DQA1等位基因不相关。所得结果表明，在DQA1和DQB1基因的顺式和反式互补的功能表达中涉及一些额外的遗传因素，其中DQ等位基因作为自我调节因子起着关键作用。
