Kollnberger Simon, Bowness Paul
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Adv Exp Med Biol. 2009;649:277-85. doi: 10.1007/978-1-4419-0298-6_21.
HLA-B27 (B27) is strongly associated with spondyloarthopathy. The classical role of B27 is to present peptides from intracellular pathogens as a heterotrimeric complex with beta2 microglobulin for recognition by the T-cell receptor (TCR) of CD8 T-cells. In addition to heterotrimers, B27 can also be expressed as cell surface beta2-microglobulin (beta2m)-free homodimers (B27(2)). In addition to the TCR, MHC class I molecules bind to immunoregulatory receptors including members of the killer immunoglobulin-like receptor (KIR) and leukocyte immunoglobulin-like receptor (LILR) families. Rodents express the paired immunoglobulin receptor (PIR) family which are related to LILR. B27(2) but not beta2m-associated B27 binds to KIR3DL2 and rodent PIR. NK and T-cells expressing the immune receptor KIR3DL2, which interacts with B27(2), are expanded in B27 AS patients. Ligation of immune receptors by B27(2) promotes the survival of KIR-expressing leukocytes and modulates immune cytokine production. Upregulation ofB272 in spondyloarthritis and differential interaction of beta2m-associated HLA-B27 and B27(2) with immune receptors could be involved in the pathogenesis of B27-associated spondyloarthritis (AS).
HLA - B27（B27）与脊柱关节病密切相关。B27的经典作用是与β2微球蛋白形成异源三聚体，呈递细胞内病原体的肽段，以供CD8 T细胞的T细胞受体（TCR）识别。除了异源三聚体，B27还可表达为无细胞表面β2微球蛋白（β2m）的同源二聚体（B27(2)）。除了TCR，MHC I类分子还与免疫调节受体结合，包括杀伤细胞免疫球蛋白样受体（KIR）家族和白细胞免疫球蛋白样受体（LILR）家族的成员。啮齿动物表达与LILR相关的配对免疫球蛋白受体（PIR）家族。B27(2)而非与β2m相关的B27与KIR3DL2和啮齿动物PIR结合。表达与B27(2)相互作用的免疫受体KIR3DL2的自然杀伤细胞（NK）和T细胞在B27强直性脊柱炎（AS）患者中扩增。B27(2)对免疫受体的连接促进了表达KIR的白细胞的存活，并调节免疫细胞因子的产生。脊柱关节炎中B27(2)的上调以及与β2m相关的HLA - B27和B27(2)与免疫受体的差异相互作用可能参与了B27相关脊柱关节炎（AS）的发病机制。
