Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation.
Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation.
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DOI：
10.1084/jem.20031560
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发表时间：
2004-04-19
影响因子：
15.3
通讯作者：
Ritz, J
中科院分区：
文献类型：
--
作者：
Zorn, E;Miklos, DB;Floyd, BH;Mattes-Ritz, A;Guo, LX;Soiffer, RJ;Antin, JH;Ritz, J
关键词：
我们研究了一名男性慢性移植物抗宿主病（GVHD）患者从人类组织相容性白细胞抗原（HLA）相同的女性同胞异基因造血干细胞移植后对DBY（一种模型H-Y次要组织相容性抗原（mHA））的免疫反应。筛选患者外周血单核细胞对代表DBY的整个氨基酸序列的一组93种肽的反应性。该表位筛选揭示了对单个DBY肽的高频CD 4 + T细胞应答，其在移植后持续8至21个月。从移植后患者细胞中建立了显示相同反应性的CD 4 + T细胞克隆，并用于将T细胞表位表征为从DBY序列中的位置30开始的19-mer肽，并由HLA-DRB 1 *1501限制。值得注意的是，相应的X同源肽也被供体T细胞识别。此外，T细胞克隆对成熟的HLA-DRB 1 *1501男性和女性树突状细胞的反应相同，表明DBY和DBX肽都是内源性加工的。移植后，患者还产生了对重组DBY蛋白特异性的抗体，并且不与DBX反应。将该抗体应答映射到从位置118和536开始的两个DBY肽。相应的DBX肽未被识别。这些研究首次证明了同种异体移植后对H-Y抗原的协调B和T细胞免疫应答。受体雄性细胞的特异性由B细胞应答介导，而不是由供体T细胞介导。这种双重DBX/DBY抗原是在慢性GVHD背景下鉴定的第一种mHA。
We examined the immune response to DBY, a model H-Y minor histocompatibility antigen (mHA) in a male patient with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant from a human histocompatibility leukocyte antigen (HLA)-identical female sibling. Patient peripheral blood mononuclear cells were screened for reactivity against a panel of 93 peptides representing the entire amino acid sequence of DBY. This epitope screen revealed a high frequency CD4+ T cell response to a single DBY peptide that persisted from 8 to 21 mo after transplant. A CD4+ T cell clone displaying the same reactivity was established from posttransplant patient cells and used to characterize the T cell epitope as a 19-mer peptide starting at position 30 in the DBY sequence and restricted by HLA-DRB1*1501. Remarkably, the corresponding X homologue peptide was also recognized by donor T cells. Moreover, the T cell clone responded equally to mature HLA-DRB1*1501 male and female dendritic cells, indicating that both DBY and DBX peptides were endogenously processed. After transplant, the patient also developed antibodies that were specific for recombinant DBY protein and did not react with DBX. This antibody response was mapped to two DBY peptides beginning at positions 118 and 536. Corresponding DBX peptides were not recognized. These studies provide the first demonstration of a coordinated B and T cell immune response to an H-Y antigen after allogeneic transplant. The specificity for recipient male cells was mediated by the B cell response and not by donor T cells. This dual DBX/DBY antigen is the first mHA to be identified in the context of chronic GVHD.
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影响因子：
4.4
作者：
Sallusto, Federica;Lanzavecchia, Antonio
通讯作者：
Lanzavecchia, Antonio
影响因子：
3.2
作者：
Falkenburg, JHF;Marijt, WAF;Willemze, R
通讯作者：
Willemze, R
影响因子：
168.9
作者：
Spierings, E;Vermeulen, CJ;Goulmy, E
通讯作者：
Goulmy, E
影响因子：
56.9
作者：
WANG, W;MEADOWS, LR;ENGELHARD, VH
通讯作者：
ENGELHARD, VH
影响因子：
82.9
作者：
Mutis, T;Gillespie, G;Goulmy, E
通讯作者：
Goulmy, E