Fernandez-Viña M A, Falco M, Gao X, Cerna M, Sun Y, Raimondi E, Stastny P
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8886.
Hum Immunol. 1994 Apr;39(4):290-8. doi: 10.1016/0198-8859(94)90272-0.
Polymorphisms outside the hypervariable regions of HLA class II alleles that do not affect the peptide-binding site are probably not under selective pressure and could therefore be useful as markers of the evolutionary pathways of the HLA class II haplotypes. We have analyzed such a polymorphism in the variants of DQA103, which differ at residue 160 encoded in exon 3. Our study included homozygous BCLs of the 10th IHWS and samples of a multiracial panel of 723 unrelated subjects which were also typed for allelic variations in exon 2 by hybridization with SSOP. BCLs having DQA103 and 131 selected DQA103-positive samples were typed for the dimorphism in exon 3 that distinguishes DQA10301 and DQA10302. DQA10301 was found to be exclusively associated with DQB10302, while samples carrying DQB10201, 0301, 0303, and 0401 always had DQA10302. A few haplotypes carrying DQB10302 had DQA10302. The fact that DQA10301 is completely included in DQB10302, and not vice versa, suggests that DQA10301 may have arisen from a mutation in a haplotype containing DQA10302-DQB10302. DQB10302 was found to be associated with all DR4 subtypes, suggesting possibly that the current variants of DRB1-DR4 may be of more recent origin. DRB10405 was the only subtype of DR4 which was not associated with DQA1*0301 and had multiple associations with the DQB1 alleles, therefore, perhaps representing the oldest allele of this group.
位于HLA II类等位基因高变区之外且不影响肽结合位点的多态性可能不受选择压力影响，因此可用作HLA II类单倍型进化途径的标记。我们分析了DQA103变体中的这种多态性，这些变体在第3外显子编码的第160位残基处存在差异。我们的研究包括第10届国际组织相容性研讨会的纯合B细胞系以及723名无关个体的多种族样本，这些样本也通过与序列特异性寡核苷酸探针（SSOP）杂交进行第2外显子的等位基因变异分型。对具有DQA103的B细胞系和131个选定的DQA103阳性样本进行第3外显子的二态性分型，以区分DQA10301和DQA10302。发现DQA10301仅与DQB10302相关，而携带DQB10201、0301、0303和0401的样本总是具有DQA10302。少数携带DQB10302的单倍型具有DQA10302。DQA10301完全包含在DQB10302中，反之则不然，这一事实表明DQA10301可能源自包含DQA10302 - DQB10302的单倍型中的突变。发现DQB10302与所有DR4亚型相关，这可能表明当前DRB1 - DR4的变体可能起源较晚。DRB10405是DR4的唯一亚型，它与DQA1*0301不相关，并且与DQB1等位基因有多种关联，因此可能代表该组中最古老的等位基因。
