Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype.
Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype.
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DOI：
10.4049/jimmunol.154.2.685
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发表时间：
1995-01
影响因子：
4.4
通讯作者：
M. D. Guercio;J. Sidney;Gary G. Hermanson;Cynthia Perez;Howard M. Grey;Ralph T. Kubo;Alessandro Sette
中科院分区：
文献类型：
--
作者：
M. D. Guercio;J. Sidney;Gary G. Hermanson;Cynthia Perez;Howard M. Grey;Ralph T. Kubo;Alessandro Sette
已经开发了用放射性标记的肽和表达HLA I类的哺乳动物细胞如EBV转化的B细胞系和PHA活化的母细胞的直接MHC结合测定。如果靶细胞在β 2-微球蛋白存在下于26 ℃预孵育过夜，则可获得放射性标记探针的显著结合。在这些条件下，由任一细胞类型表达的高达百分之几的HLA分子可以被标记的肽结合。用这些测定法，检测了A*0201限制的B型肝炎病毒核心18-27肽与其它A2亚型的交叉反应性程度。确定该肽表位也结合A*0202、A*0205和A*0206，但不结合A*0207亚型。用合成肽类似物的抑制实验强调了HLA-A*0201、A*0202和A*0205等位基因的相似配体特异性。对有助于形成各种HLA等位基因的B和F口袋的多态性残基的分析允许预测肝炎B病毒核心18-27表位与两个其它HLA等位基因（HLA-A*6802和A*6901）的结合。因此，似乎一个家族的至少六个不同的HLA-A分子可以共享重叠的配体特异性（在位置2和在C末端的脂肪族残基）。这些结果表明，广泛的交叉反应性肽表位可以被识别，并大大提高了基于肽的疫苗接种方法的可行性。
Direct MHC binding assays with radiolabeled peptides and HLA class I-expressing mammalian cells such as EBV-transformed B cell lines and PHA-activated blasts have been developed. Significant binding of the radiolabeled probe could be obtained if the target cells were preincubated overnight at 26 degrees C in the presence of beta 2-microglobulin. Under these conditions, up to a few percent of the HLA molecules expressed by either cell type could be bound by the labeled peptides. With these assays, the degree of cross-reactivity of the A*0201-restricted hepatitis B virus core 18-27 peptide with other A2 subtypes was examined. It was determined that this peptide epitope also binds the A*0202, A*0205, and A*0206 but not A*0207 subtypes. Inhibition experiments with panels of synthetic peptide analogues underlined the similar ligand specificities of the HLA-A*0201, A*0202, and A*0205 alleles. Analysis of the polymorphic residues that help form the B and F pockets of various HLA alleles allowed prediction of binding of the hepatitis B virus core 18-27 epitope to two other HLA alleles (HLA-A*6802 and A*6901). Thus, it appears that a family of at least six different HLA-A molecules may share overlapping ligand specificities (aliphatic residues in position 2 and at the C termini). These results suggest that broadly cross-reactive peptide epitopes can be identified and greatly enhance the prospective feasibility of peptide-based vaccination approaches.