Sheehy M J, Meske L M, Emler C A, Rowe J R, Neme de Gimenez M H, Ingle C A, Chan A, Trucco M, Mak T W
American Red Cross Blood Services, Madison, WI 53705.
Hum Immunol. 1989 Dec;26(4):261-71. doi: 10.1016/0198-8859(89)90004-9.
We performed a multiple-affected-sib study to determine if T-cell receptor alpha-chain alleles affect susceptibility to insulin-dependent diabetes mellitus. Restriction fragment length polymorphisms were used to follow the segregation of allelic T-cell receptor alpha complexes within the families. The segregation of T-cell receptor alpha alleles in 29 multiplex families revealed no significant tendency for affected sibs to share T-cell receptor alpha-chain alleles more often than would be expected by chance alone (p greater than 0.2). In contrast, the same type of analysis for HLA alleles easily detected the well-known linkage of insulin-dependent diabetes mellitus susceptibility to the HLA complex (p = 0.003). We suggest that the importance of HLA alleles in insulin-dependent diabetes mellitus susceptibility and the lack of importance of T-cell receptor alpha alleles result from the different strategies by which HLA and T-cell receptor molecules achieve antigen-binding diversity: multiple loci and allelic diversity in the case of HLA; combinatorial, junctional, and N-region diversity in the case of the T-cell receptor. In this paper we also describe three new restriction fragment length polymorphisms of the T-cell receptor alpha complex and a new method for testing the significance of linkage in multiple-affected-sib studies.
我们开展了一项多患病同胞研究，以确定T细胞受体α链等位基因是否影响胰岛素依赖型糖尿病的易感性。采用限制性片段长度多态性来追踪家族内等位基因T细胞受体α复合体的分离情况。对29个多个患病同胞的家庭中T细胞受体α等位基因的分离分析显示，患病同胞共享T细胞受体α链等位基因的频率并无显著高于仅由随机因素预期的频率的倾向（p>0.2）。相比之下，对HLA等位基因进行的相同类型分析很容易检测到胰岛素依赖型糖尿病易感性与HLA复合体之间众所周知的连锁关系（p = 0.003）。我们认为，HLA等位基因在胰岛素依赖型糖尿病易感性中的重要性以及T细胞受体α等位基因的非重要性，源于HLA和T细胞受体分子实现抗原结合多样性的不同策略：HLA为多个基因座和等位基因多样性；T细胞受体为组合、连接和N区多样性。在本文中，我们还描述了T细胞受体α复合体的三种新的限制性片段长度多态性以及一种在多患病同胞研究中检验连锁显著性的新方法。
