The humoral immune response against an HLA class I allodeterminant correlates with the HLA-DR phenotype of the responder.
The humoral immune response against an HLA class I allodeterminant correlates with the HLA-DR phenotype of the responder.
复制标题
针对 HLA I 类同种异体决定簇的体液免疫反应与应答者的 HLA-DR 表型相关。
DOI：
10.1097/00007890-199907270-00002
复制
发表时间：
1999
期刊：
影响因子：
6.2
通讯作者：
Fuller,A
中科院分区：
文献类型：
--
作者：
Fuller,TC;Fuller,A
背景：控制针对外源 HLA 组织相容性抗原的同种抗体反应的遗传基础从未被阐明。最可能的假设是，宿主的 HLA II 类同种抗原通过其呈现加工过的 HLA 同种肽片段的能力来调节反应，以实现 CD4+ T 淋巴细胞和 B 淋巴细胞之间的同源相互作用，从而导致 IgG 抗体合成。方法。我们分析了我们的同种异体致敏移植患者群体对血清学定义的体液反应性 公共 HLA I 类表位，Bw4。合成了代表 Bw4 表位（氨基酸 74-86）和替代 Bw6 表位的线性序列的肽，并使用定量荧光结合测定法测定了与一组 HLA 纯合淋巴母细胞 B 细胞的结合。结果。我们发现，73% 产生 HLA-Bw4 特异性同种抗体的患者表达 HLA-DRB1*01或HLA-DRB1*03同种抗原；其余应答者中有 19% 表达 HLA-DRB1* 04。器官共享移植登记联合网络的分析表明，在致敏的 DRB1* 01+ 或 DRB1* 03+ 受者中，Bw4 不匹配的尸体肾同种异体移植物的存活率显着降低（P < 0.01）。在体外，Bw4 肽与 DRB1* 01+ 和 DRB1* 03+ 淋巴母细胞 B 细胞强烈结合； Bw6 肽没有观察到类似的结合。这些发现通过使用 HLA-DR α/β 基因转染的小鼠成纤维细胞系以及使用纯化的 HLA-DR 同种抗原的固相酶联免疫吸附测定得到证实。结论。我们得出的结论是，至少有两个人类 Ir 基因，HLA-DRB1* 01 和 HLA-DRB1* 03，赋予两种体液免疫缺陷的高风险。 HLA-Bw4 不相容情况下的同种异体过敏和同种异体肾移植失败。这些发现可能有助于未来设计新的抗原匹配策略，以降低体液 HLA 同种异体致敏和慢性同种异体移植排斥的风险。
Background.The genetic basis for control of alloantibody responses against foreign HLA histocompatibility antigens has never been delineated. The most likely postulate would be that HLA class II alloantigens of the host regulate the response through their ability to present processed HLA allopeptide fragments for the cognate interaction between CD4+ T lymphocytes and B lymphocytes that leads to IgG antibody synthesis.Methods.We have analyzed our allosensitized transplant patient population with regard to humoral responsiveness to a serologically defined public HLA class I epitope, Bw4. Peptides representing the linear sequence of the Bw4 epitope (amino acids 74-86) and the alternative Bw6 epitope were synthesized and assayed for binding to a panel of HLA homozygous lymphoblastoid B cells using a quantitative fluorescence binding assay.Results.We found that 73% of patients who have produced a HLA-Bw4-specific alloantibody express either the HLA-DRB1* 01 or HLA-DRB1* 03 alloantigen; 19% of the remaining responders expressed HLA-DRB1* 04. Analysis of the United Network for Organ Sharing Transplant Registry indicated that the survival of cadaver renal allografts mismatched for Bw4 was significantly compromised in sensitized DRB1* 01+ or DRB1* 03+ recipients (P< 0.01). In vitro, the Bw4 peptide bound strongly to DRB1* 01+ and DRB1* 03+ lymphoblastoid B cells; no similar binding was observed with Bw6 peptide. These findings were confirmed using murine fibroblast lines transfected with HLA-DR α/β genes and by solid-phase enzyme-linked immunosorbent assay using purified HLA-DR alloantigen.Conclusions.We conclude that there are at least two human Ir genes, HLA-DRB1* 01 and HLA-DRB1* 03, that confer a high risk for both humoral allosensitization and renal allograft failure in situations of HLA-Bw4 incompatibility. These findings may be of future benefit in devising new antigen matching strategies for reducing the risk of humoral HLA allosensitization and chronic allograft rejection.