Ozen S, Clayberger C, Krensky A M, Benjamin R
Stanford University School of Medicine, Department of Pediatric Nephrology and Cell Biology, Palo Alto, California.
Clin Exp Rheumatol. 1992 Nov-Dec;10(6):583-7.
The three-dimensional structure of the HLA class I molecules has highlighted the importance of the "groove" formed by the helices. We used site-directed mutagenesis to construct a series of HLA-B27 mutants with different substitutions at the sites of the conserved amino acid residues of HLA-B27 subtypes, specifically residue 77 which is thought to be critical to the binding site of the molecule, and a residue at the CD8 binding site. We formed an anti-B27 CTL line and derived six anti-B27 clones. Each of the six clones showed a different pattern of reaction, reflecting the diversity of the epitopes recognized. All nine mutants were effective in altering allorecognition by HLA-B27 specific CTL, although positions 45 and 77 caused the most drastic effect. The residue in position 77 is also the last amino acid of the peptide sequence shared with Klebsiella. Our results highlight the importance of certain epitopes in allorecognition that may have important implications for the immunotherapy of autoimmune diseases.
HLA I类分子的三维结构突出了由螺旋形成的“凹槽”的重要性。我们使用定点诱变构建了一系列HLA - B27突变体，这些突变体在HLA - B27亚型保守氨基酸残基位点有不同的替换，特别是被认为对分子结合位点至关重要的第77位残基，以及CD8结合位点的一个残基。我们构建了一条抗B27 CTL细胞系并获得了六个抗B27克隆。六个克隆中的每一个都表现出不同的反应模式，反映了所识别表位的多样性。所有九个突变体都能有效改变HLA - B27特异性CTL的同种异体识别，尽管第45位和第77位残基产生的影响最为显著。第77位残基也是与克雷伯菌共有的肽序列的最后一个氨基酸。我们的结果突出了某些表位在同种异体识别中的重要性，这可能对自身免疫性疾病的免疫治疗具有重要意义。
