Significance of the HLA molecular structure to transplantation.
Significance of the HLA molecular structure to transplantation.
复制标题
HLA分子结构对移植的意义。
DOI：
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发表时间：
1988
期刊：
影响因子：
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通讯作者：
Cecka Jm
中科院分区：
文献类型：
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作者：
M. Park;P. Terasaki;A. Barbetti;H. Han;Cecka Jm
1. HLA-A、B、C 的第一、第二和第三结构域以及 DR β、DQ α 和 DQ β 分子的第一结构域中的残基已被指定为来自已知氨基酸序列的独特 A、B、C 或 DR 特异性。注意到抗体与大多数这些可变氨基酸残基相关。 2.因此，我们得出结论，第一结构域中的大多数可变残基充当免疫原，针对其引发了抗体。 3.如果这些位置的变异是免疫原，那么移植匹配应该通过考虑不匹配的氨基酸而不是像今天所执行的私人特异性来进行。 4. 由于许多特异性尚未测序，因此无法立即对 HLA-A、B、C 特异性进行分子匹配。对于 DR 和 DQ 特异性，序列已确定，但识别 DR 和 DQ 亚型的抗血清现在才可用。一旦对患者进行了 23 个 DR β 等位基因、8 个 DQ α 等位基因和 13 个 DQ β 等位基因的分型，匹配应该是可行的。 5. 分子匹配结合了公共和私人特异性匹配，因为它假设两种类型的抗原是不同的。单个扩展的 DR 错配可能涉及多达 76 个氨基酸残基的错配。 6. HLA 分子真正的交叉反应性最终可以通过结构研究确定。前面描述的大多数“交叉反应”可能是共同的决定因素。
1. Residues in the first, second, and third domains of HLA-A,B,C, and the first domain of DR beta, DQ alpha, and DQ beta molecule have been assigned to unique A,B,C or DR specificities from the known amino acid sequences. Antibodies were noted to correlate with most of these variable amino acid residues. 2. We therefore conclude that most of the variable residues in the first domain function as immunogens against which the antibodies had been elicited. 3. If the variants at these positions are immunogens, then it follows that matching for transplantation should be done by considering mismatched amino acids rather than the private specificities, as performed today. 4. Molecular matching cannot be performed immediately for the HLA-A,B,C specificities since many specificities are not yet sequenced. For the DR and DQ specificities, the sequences are established, but antisera identifying the subtypes of DR and DQ are only now becoming available. Once patients are typed for the 23 DR beta alleles, 8 DQ alpha alleles and 13 DQ beta alleles, matching should be feasible. 5. Molecular matching combines both public and private specificity matching since it assumes that both types of antigens are distinct. A single extended DR mismatch may involve as many as 76 amino acid residues of mismatch. 6. True cross-reactivity of the HLA molecules can eventually be established through structural studies. Most of the previously described "cross-reactivities" are likely to be shared determinants.