Keever C A, Leong N, Cunningham I, Copelan E A, Avalos B R, Klein J, Kapoor N, Adams P W, Orosz C G, Tutschka P J
Bone Marrow Transplantation Division, Ohio State University, Columbus.
Bone Marrow Transplant. 1994 Jul;14(1):137-45.
We describe the recipient of a marrow graft from an HLA-serologically identical unrelated donor from whom highly potent host-reactive CTL of donor origin were isolated in association with acute GVHD. Extensive sequence and biochemical analysis of the HLA complex of this donor and recipient revealed several disparities in class I and class II HLA with the potential to be recognized by T cells from the donor or the host. The donor-derived CTL exclusively recognized a class I HLA difference associated with HLA-B44. Nucleotide sequencing of donor and recipient cells revealed that the patient possessed the HLA-B4402 allele recognized by IEF as B44.2 while the donor possessed HLA-B4403 (IEF variant B44.1). These alleles differ at one amino acid residue located at position 156 in the alpha 2 domain. The donor-derived CTL were shown to be specific for B44.2 by blocking studies and by the lysis of five different B44.2+ unrelated cell lines, two of which were confirmed by sequencing to be homozygous for B4402. A host-specific difference involving a HLA-DRB1 allele was not recognized by the CTL, neither did HLA differences unique to the donor HLA-B4403 and HLA-DQ8 elicit a host response. These data show that certain HLA disparities may be tolerated at the same time that other disparities elicit a potent immunologic response. The chemical nature of the difference, its structural impact, as well as the conditions of transplant appear to influence the type of response which occurs.
我们描述了一名接受来自HLA血清学相同的无关供者骨髓移植的受者，在急性移植物抗宿主病（GVHD）发生时，从该供者体内分离出了高效的宿主反应性供者来源的细胞毒性T淋巴细胞（CTL）。对该供者和受者的HLA复合体进行广泛的序列和生化分析发现，I类和II类HLA存在一些差异，这些差异有可能被供者或宿主的T细胞识别。供者来源的CTL仅识别与HLA - B44相关的I类HLA差异。供者和受者细胞的核苷酸测序显示，患者拥有被等电聚焦（IEF）识别为B44.2的HLA - B4402等位基因，而供者拥有HLA - B4403（IEF变体B44.1）。这些等位基因在α2结构域第156位的一个氨基酸残基处存在差异。通过阻断研究以及对五种不同的B44.2 +无关细胞系的裂解实验表明，供者来源的CTL对B44.2具有特异性，其中两种细胞系经测序证实为B4402纯合子。CTL未识别涉及HLA - DRB1等位基因的宿主特异性差异，供者特有的HLA - B4403和HLA - DQ8差异也未引发宿主反应。这些数据表明，某些HLA差异可能被耐受，而其他差异则会引发强烈的免疫反应。差异的化学性质、其结构影响以及移植条件似乎会影响所发生的反应类型。
