Identification of T-cell epitopes on the rhesus polypeptides in autoimmune hemolytic anemia
Identification of T-cell epitopes on the rhesus polypeptides in autoimmune hemolytic anemia
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DOI：
10.1182/blood.v90.7.2701.2701_2701_2715
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发表时间：
1997-10-01
期刊：
影响因子：
20.3
通讯作者：
Elson, CJ
中科院分区：
文献类型：
--
作者：
Barker, RN;Hall, AM;Elson, CJ
我们先前已经表明，恒河猴（Rh）多肽是自身免疫性溶血性贫血（AIHA）患者中致病性抗红细胞（RBC）自身抗体的最常见靶标。目前工作的目的是确定这些患者的活化T细胞是否也对这些蛋白质上的表位产生回忆反应。合成了两组重叠的15-mer肽，对应于与D和Cc/Ee血型抗原表达相关的30-kD ph蛋白的序列，并筛选了刺激9例AIHA患者外周血或脾脏单核细胞体外增殖的能力。选择有利于先前激活的T细胞的回忆增殖而不是初级应答的培养条件。在7名患者中，包括所有4名ph蛋白自身抗体患者，两种或两种以上的肽引起了增殖，但来自9名其他贫血患者中的8名和9名健康供体中的7名的细胞对这些小组没有反应。多个肽在两个阳性对照供体中也是刺激性的，所述供体已经用ph D阳性RBC同种免疫。六种不同的肽谱在AIHA患者中引起了反应，这种变化可能反映了该组中不同的HLA类型。刺激肽被确定在整个域之间共享的，或特定的，每个相关的30-kD Rh蛋白，但T细胞，响应非保守区域没有交叉反应的替代序列。抗主要组织相容性复合体的第1类抗体阻断的反应和耗竭实验证实，增殖的单核细胞的T细胞。值得注意的是，针对多种Rh肽增殖的脾T细胞也对完整的RBC有反应。我们提出，在许多情况下，AIHA的致病性自身抗体的产生是由T辅助细胞的激活驱动的，该细胞对以前的Rh蛋白上的隐蔽表位具有特异性。(C)1997年，美国血液学会。
We have shown previously that the Rhesus (Rh) polypeptides are the commonest targets for pathogenic anti-red blood cell (RBC) autoantibodies in patients with autoimmune hemolytic anemia (AIHA). The aim of the current work was to determine whether activated T cells from such patients also mount recall responses to epitopes on these proteins. Two panels of overlapping 15-mer peptides, corresponding to the sequences of the 30-kD ph proteins associated with expression of the D and Cc/Ee blood group antigens, were synthesized and screened for the ability to stimulate the in vitro proliferation of mononuclear cells from the peripheral blood or spleen of nine AIHA cases. Culture conditions were chosen that favor recall proliferation by previously activated T cells, rather than primary responses. In seven of the patients, including all four cases with autoantibody to the ph proteins, two or more peptides elicited proliferation, but cells from eight of nine patients with other anemias and seven of nine healthy donors failed to respond to the panels. Multiple peptides were also stimulatory in two positive control donors who had been alloimmunized with ph D-positive RBCs. Six different profiles of peptides elicited responses in the AIHA patients, and this variation may reflect the different HLA types in the group. Stimulatory peptides were identified throughout domains shared between, or specific to, each of the related 30-kD Rh proteins, but T cells that responded to nonconserved regions did not crossreact with the alternative sequences. Anti-major histocompatibility complex class tl antibodies blocked the responses and depletion experiments confirmed that the proliferating mononuclear cells were T cells. Notably, splenic T cells that proliferated against multiple Rh peptides also responded to intact RBCs. We propose that pathogenic autoantibody production in many cases of AIHA is driven by the activation of T-helper cells specific for previously cryptic epitopes on the Rh proteins. (C) 1997 by The American Society of Hematology.