López de Castro J A, Bragado R, Lauzurica P, López D, Rojo S
Department of Immunology, Fundación Jiménez Díaz, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Madrid, Spain.
Scand J Rheumatol Suppl. 1990;87:21-31. doi: 10.3109/03009749009097054.
HLA-B27 is strongly associated with susceptibility to ankylosing spondylitis and other spondyloarthropathies. Structural analysis of this antigen has revealed the existence of multiple variants, or subtypes, in human populations. The structural microheterogeneity of these subtypes deeply affects allospecific T cell recognition and most of it occurs at an spatial cluster within the peptide binding groove of the molecule. Many polymorphic residues whose combination is unique to HLA-B27 but is conserved among subtypes are clustered in a spatially separated site of the groove from that where most subtype polymorphism occurs. Site-directed mutagenesis and DNA-mediated gene transfer has been used to show that the positions that are polymorphic among subtypes are highly relevant for modulating T cell recognition, so that immunologically silent changes do not occur. These studies have also revealed an extremely high clonotypic diversity in the alloreactive response against HLA-B27. The structural basis for this diversity has been examined by sequencing the clonotypic T cell receptors. The analysis shows a certain bias in V beta gene segment usage, as well as other recurrent structural motives, among T cell receptor beta chains from HLA-B27-specific cytotoxic T cell clones.
HLA - B27与强直性脊柱炎及其他脊柱关节病的易感性密切相关。对该抗原的结构分析显示，人类群体中存在多种变体或亚型。这些亚型的结构微异质性深刻影响同种异体特异性T细胞识别，且大部分发生在分子肽结合槽内的一个空间簇中。许多多态性残基的组合是HLA - B27特有的，但在各亚型中保守，它们聚集在槽内与大多数亚型多态性发生位点在空间上分离的位置。定点诱变和DNA介导的基因转移已被用于表明，各亚型间多态性的位置与调节T细胞识别高度相关，因此不会发生免疫沉默变化。这些研究还揭示了针对HLA - B27的同种异体反应中极高的克隆型多样性。通过对克隆型T细胞受体进行测序，研究了这种多样性的结构基础。分析表明，在来自HLA - B27特异性细胞毒性T细胞克隆的T细胞受体β链中，Vβ基因片段的使用存在一定偏差，以及其他反复出现的结构基序。
