Gao X M, Wordsworth P, McMichael A
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB.
Eur J Immunol. 1994 Jul;24(7):1665-70. doi: 10.1002/eji.1830240731.
Both ankylosing spondylitis (AS) and reactive arthritis (ReA) are strongly associated with HLA-B27 although the mechanism for this association is still unknown. Here we examine the hypothesis that B27-restricted, joint antigen-specific cytotoxic T lymphocytes (CTL) may be the driving force of AS and ReA. Type II and type XI procollagens (CII and CXI, respectively), expressed almost exclusively in the articular cartilage of the joints, were chosen as the possible targets of autoimmune CTL. Type I procollagen (CI), expressed in many different tissues, was also included as control. Nineteen nonamer peptides bearing appropriate HLA-B27 binding motifs from human CI, CII and CXI were identified and synthesized. When analyzed for binding affinity to HLA-B27 in assembly assays, four (two from CII, two from CXI) were found capable of binding to HLA-B27 with high affinity. These B27-binding collagen peptides were then used to stimulate peripheral blood lymphocytes from eight B27-positive AS and three ReA patients for identification of possible B27-restricted autoimmune CTL. HLA-B27-restricted CTL specific for one of the CII peptides, P109 were found in one of the ReA patients, but in none of the others.
强直性脊柱炎（AS）和反应性关节炎（ReA）均与HLA - B27密切相关，尽管这种关联的机制尚不清楚。在此，我们检验这样一种假说：B27限制性、关节抗原特异性细胞毒性T淋巴细胞（CTL）可能是AS和ReA的驱动因素。分别几乎仅在关节的关节软骨中表达的II型和XI型前胶原（分别为CII和CXI）被选为自身免疫性CTL的可能靶标。在许多不同组织中表达的I型前胶原（CI）也作为对照被纳入。从人CI、CII和CXI中鉴定并合成了19个带有合适HLA - B27结合基序的九聚体肽。在组装试验中分析它们与HLA - B27的结合亲和力时，发现其中四个（两个来自CII，两个来自CXI）能够以高亲和力结合HLA - B27。然后用这些与B27结合的胶原肽刺激八名B27阳性AS患者和三名ReA患者的外周血淋巴细胞，以鉴定可能的B27限制性自身免疫性CTL。在一名ReA患者中发现了对CII肽之一P109具有特异性的HLA - B27限制性CTL，但在其他患者中均未发现。
