Alloresponses to HLA-DP detected in the primary MLR: Correlation with a single amino acid difference
Alloresponses to HLA-DP detected in the primary MLR: Correlation with a single amino acid difference
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DOI：
10.1016/s0198-8859(97)00091-8
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发表时间：
1997-07-01
期刊：
影响因子：
2.7
通讯作者：
Tait, BD
中科院分区：
文献类型：
--
作者：
Nicholson, I;Varney, M;Tait, BD
在 50 个 HLA-A、B、DR 和 DQ 相同对中双向测量单向混合淋巴细胞反应 (MLR-1) 反应，并研究 DP 在 MLR 刺激中的作用。通过聚合酶链式反应序列特异性寡分型 (PCR-SSO) 技术在等位基因水平上进行 DR、DQ 和 DP 分型。该团体由 19 名潜在的骨髓移植受者和 34 名无关的捐赠者组成。当一名患者有不止一名匹配的供体时，还对供体/供体 MLR-1 进行研究。在 50 对中的 3 对 (6%) 中观察到 DP 同一性，然而，由于纯合性，在 100 个病例中的 21 个 (21%) 中，刺激细胞中不存在不相容性。零个 DPB1 错配与 1 个 (p = 0.002) 和 2 个 (p = 0.02) DPB1 错配之间的相对反应 (RR) 范围存在显着差异：零 DPB1 错配组中 52.4% 的病例 RR < 1.0%，而 1 个和 2 个 DPB1 错配组中这一比例为 31.6% 和 27.3%。 DPB1*0201和0301刺激产生最高的RR（分别为12.9+/-22.5和17.5+/-17.0），而DPB1*0401和0402刺激导致低水平的T细胞反应（分别为1.3+/-8.2和0.6+/-11.5）。当反应仅限于 DPB1*0401 纯合子以标准化反应者类型时，获得了类似的结果 (DPB1*0201 v DPB1*0402 p = 0.008)。 DPB1*0201 和 0402 等位基因的蛋白质产物在第 69 位有一个氨基酸不同（DPB1*0402-赖氨酸，DPB1*0201-谷氨酸）。进行了进一步的分析，因此将反应者和刺激者评分为谷氨酸阳性（E+）或阴性（E-）。与 E- 刺激器相比，对 E+ 刺激器的反应显着增加 (p = 0.004)。 E+刺激器组与E-响应者/E-刺激器亚组(p = 0.012)和E+响应者/E-刺激器(p = 0.009)之间的相对响应分布也存在显着差异。然而，第 69 位的氨基酸差异并不能解释 MLR-1 中 DP 引起的所有反应，如在 DPB1*0301（赖氨酸位置）是刺激细胞上唯一差异的情况下观察到的强烈反应所证明的那样。结果表明，并非所有 DP 不相容性都会引发可测量的 T 细胞 MLR 反应，但在确实发生反应的情况下，DP 第一个结构域中的残基 69 似乎是关键的。这些结果可能对骨髓移植中的 GVHD 产生影响。 (C) 美国组织相容性和免疫遗传学学会，1997 年。由 Elsevier Science Inc. 出版。
The one-way mixed lymphocyte reaction (MLR-1) response was measured in both directions in 50 HLA-A, B, DR and DQ identical pairs and the role of DP studied in MLR stimulation. DR, DQ and DP typing was performed at the allele level by the polymerase chain reaction-sequence specific oligotyping (PCR-SSO) technique. The group consisted of 19 potential bone marrow transplant recipients and 34 marched unrelated donors. When more than one matched donor was available for a patient, donor/donor MLR-1 was also studied. DP identity was observed in 3 out of 50 pairs (6%), however due to homozygosity no incompatibility was present in the stimulating cells in 21 out of 100 cases (21%). There was a significant difference in the range of relative responses (RR) between zero DPB1 mismatches and one (p = 0.002) and two (p = 0.02) DPB1 mismatches: 52.4% of cases in the zero DPB1 mismatch group had RR < 1.0% compared with 31.6% and 27.3% in the one and two DPB1 mismatches. Stimulation by DPB1*0201 and 0301 gave the highest RR (12.9 +/- 22.5 and 17.5 +/- 17.0, respectively) while stimulation with DPB1*0401 and 0402 resulted in low levels of T cell response (1.3 +/- 8.2 and 0.6 +/- 11.5, respectively). When the responses were restricted to DPB1*0401 homozygotes to standardise for responder type similar results were obtained (DPB1*0201 v DPB1*0402 p = 0.008). The protein products of the DPB1*0201 and 0402 alleles differ by a single amino acid at position 69 (DPB1*0402-Lysine, DPB1*0201-glutamic acid). A further analysis was performed therefore scoring responders and stimulators as glutamic acid positive (E+) or negative (E-). There was a highly significant increase in the response to E+ stimulators compared with E- stimulators (p = 0.004). There was also a significant difference in the distribution of relative responses between the E+ stimulator group and the subgroups of E- responders/E-stimulators (p = 0.012) and E+ responders/E- stimulators (p = 0.009). However the amino acid difference at position 69 does not explain all responses due to DP in the MLR-1 as evidenced by the strong responses observed in cases where DPB1*0301 (lysine pos.) was the only difference on the stimulator cells. The results indicate that not all DP incompatibilities elicit a measurable T cell MLR response, but where a response does occur residue 69 in the first domain of DP appears to be pivocal. These results may have implications with respect to GVHD in bone marrow transplantation. (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc.