Kwok W W, Domeier M L, Raymond F C, Byers P, Nepom G T
Virginia Mason Research Center, Seattle, WA 98101, USA.
J Immunol. 1996 Mar 15;156(6):2171-7.
Polymorphic residues of HLA class II molecules influence immune activation in part by determining specific structural constraints for binding antigenic peptides. We identified a peptide from glutamic acid decarboxylase, a diabetes-associated autoantigen that preferentially bound to HLA-DQ3.2 molecules, one of the HLA determinants highly associated with insulin-dependent diabetes. We analyzed interactions of specific HLA-DQ residues with modified peptide analogues and found a pattern of permissive site-specific amino acids that accommodated allele-specific binding. Four anchor residues constrain binding to different DQ alleles; limited variation at two of these sites, residues 4 and 9, accounts for the unique pattern of peptide binding to HLA-DQ3.1 or HLA-DQ3.2.
HLA II类分子的多态性残基部分地通过确定结合抗原肽的特定结构限制来影响免疫激活。我们鉴定出一种来自谷氨酸脱羧酶的肽，谷氨酸脱羧酶是一种与糖尿病相关的自身抗原，它优先结合HLA-DQ3.2分子，HLA-DQ3.2是与胰岛素依赖型糖尿病高度相关的HLA决定簇之一。我们分析了特定HLA-DQ残基与修饰肽类似物的相互作用，发现了一种允许位点特异性氨基酸的模式，该模式适应等位基因特异性结合。四个锚定残基限制了与不同DQ等位基因的结合；其中两个位点（残基4和9）的有限变异解释了肽与HLA-DQ3.1或HLA-DQ3.2结合的独特模式。
