CRUCIAL ROLE OF THE 3RD AND 4TH HYPERVARIABLE REGIONS OF HLA-DPB1 ALLELIC SEQUENCES IN THE MIXED LYMPHOCYTE-REACTION
CRUCIAL ROLE OF THE 3RD AND 4TH HYPERVARIABLE REGIONS OF HLA-DPB1 ALLELIC SEQUENCES IN THE MIXED LYMPHOCYTE-REACTION
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DOI：
10.1016/0198-8859(92)90072-u
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发表时间：
1992-03-01
期刊：
影响因子：
2.7
通讯作者：
BIGNON, JD
中科院分区：
文献类型：
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作者：
CESBRON, A;MOREAU, P;BIGNON, JD
由于已知HLA-DP错配诱导MLR I的增殖反应，我们研究了不同DP等位基因的真实的影响以及DPB等位基因序列的一个或几个高变区的可能作用。 因此，我们在HLA-A、B、DR、DQ和Dw相同的个体之间进行了MLR I，所述个体在DNA扩增后进行DP寡分型。 因此，在52个MLR I中评价了总共23个显示9种不同DP特异性的单DP错配的健康刺激和应答细胞。 这使我们能够独立于其他五个高变区中的氨基酸匹配或错配来分析六个高变区中的每一个的氨基酸组成的影响。 我们在此表明，在第三（C）和第四（D）高变区中共享相同氨基酸序列的DP组合与体外低增殖反应相关（p < 0.01）。 这些数据表明，一个完美的HLA-DP匹配可能不是必需的选择骨髓供体。 事实上，供体的选择可能依赖于确定尤其涉及GvHD方向的DP等位基因之间的这些特定错配HVR。 包括前瞻性DP寡分型在内的这一政策应该引起极大的兴趣，特别是当MLR I为假阴性或不可评价时。 这将能够更好地定义哪些DP失配在BMT中是可接受的。
Since HLA-DP mismatches are known to induce proliferative response in MLR I, we investigated the real impact of the different DP alleles and the possible role of one or several hypervariable regions of the DPB allelic sequences. Accordingly, we performed MLR I between HLA-A, B, DR, DQ, and Dw identical individuals DP oligotyped after DNA amplification. A total of 23 one-DP-mismatched healthy stimulator and responder cells displaying nine different DP specifities were thus evaluated in 52 MLRs I. This allowed us to analyze the impact of amino acid composition of each of the six hypervariable regions independently of the amino acid matching or mismatching in the five others. We show here that DP combinations sharing the same amino acid sequence in the third (C) and fourth (D) hypervariable regions are associated with a low proliferative response in vitro (p < 0.01). These data imply that a perfect HLA-DP matching may not be requisite in selecting bone marrow donors. Indeed, the choice of donors may rely on determination of these particular mismatched HVRs between the DP alleles involved especially in GvHD direction. This policy including prospective DP oligotyping should be of great interest, especially when MLRs I are false negative or nonevaluable. It will enable a better definition of which DP mismatches are acceptable in BMT.