Nicholson I, Varney M, Kanaan C, Grigg A, Szer J, Tiedemann K, Tait B D
Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Hum Immunol. 1997 Jul;55(2):163-9. doi: 10.1016/s0198-8859(97)00091-8.
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 matched 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 DPB10201 and 0301 gave the highest RR (12.9 +/- 22.5 and 17.5 +/- 17.0, respectively) while stimulation with DPB10401 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 DPB10401 homozygotes to standardise for responder type similar results were obtained (DPB10201 v DPB10402 p = 0.008). The protein products of the DPB10201 and 0402 alleles differ by a single amino acid at position 69 (DPB10402--Lysine, DPB10201--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 pivotal. These results may have implications with respect to GVHD in bone marrow transplantation.
在50对HLA - A、B、DR和DQ完全相同的个体中双向检测单向混合淋巴细胞反应（MLR - 1），并研究DP在MLR刺激中的作用。采用聚合酶链反应 - 序列特异性寡核苷酸分型（PCR - SSO）技术在等位基因水平进行DR、DQ和DP分型。该组包括19名潜在的骨髓移植受者和34名匹配的无关供者。当一名患者有多个匹配供者时，也研究供者/供者的MLR - 1。50对中有3对（6%）观察到DP完全相同，但由于纯合性，100例中有21例（21%）刺激细胞中不存在不相容性。DPB1错配数为零与错配数为一（p = 0.002）和二（p = 0.02）时，相对反应范围（RR）有显著差异：DPB1错配数为零的组中52.4%的病例RR < 1.0%，而DPB1错配数为一和二的组中分别为31.6%和27.3%。由DPB10201和0301刺激产生的RR最高（分别为12.9±22.5和17.5±17.0），而用DPB10401和0402刺激导致T细胞反应水平较低（分别为1.3±8.2和0.6±11.5）。当反应仅限于DPB10401纯合子以标准化反应者类型时，得到了类似的结果（DPB10201对DPB10402，p = 0.008）。DPB10201和0402等位基因的蛋白质产物在第69位氨基酸处有一个氨基酸差异（DPB10402 - 赖氨酸，DPB10201 - 谷氨酸）。因此进行了进一步分析，将反应者和刺激者分为谷氨酸阳性（E +）或阴性（E -）。与E -刺激者相比，对E +刺激者的反应有极显著增加（p = 0.004）。E +刺激者组与E -反应者/E -刺激者亚组（p = 0.012）和E +反应者/E -刺激者亚组（p = 0.009）之间的相对反应分布也有显著差异。然而，第69位氨基酸差异并不能解释MLR - 1中所有由DP引起的反应，如在刺激细胞上唯一的差异是DPB1*0301（赖氨酸阳性）的病例中观察到的强烈反应所证明的。结果表明，并非所有DP不相容性都能引发可测量的T细胞MLR反应，但在确实发生反应的情况下，DP第一结构域中的第69位残基似乎起关键作用。这些结果可能对骨髓移植中的移植物抗宿主病有影响。
