McCutcheon J A, Smith K D, Valenzuela A, Aalbers K, Lutz C T
Department of Pathology, University of Iowa, Iowa City 52242.
Hum Immunol. 1993 Feb;36(2):69-75. doi: 10.1016/0198-8859(93)90108-d.
We examine the effect of mutations in the HLA-B0702 alpha 1 domain on the binding of several well-characterized monoclonal antibodies. BB7.1 recognizes the alpha-helix, with a special requirement for residue 67. Combined with an established requirement for the alpha 2 alpha-helix, BB7.1 appears to span the B0702 peptide-binding groove. Alternatively, BB7.1 epitope conformation may be altered by distant B0702 sites. ME1 and B27M1 recognize connecting loop residues 41 and 43 and alpha 1 alpha-helical residues 67-71. Instead of contacting residue 67-71 side chains directly, however, ME1 appears to recognizes a B0702 configuration that depends upon the proper interaction of these and other HLA residues. In addition to solvent-accessible residues 41 and 43, the B27M1 epitope depends on solvent-inaccessible residue 32 at the bottom of the peptide-binding groove. MB40.2, known to require residues 169-182 near the alpha 2-alpha 3 junction, also requires the proper combination of distant residues in the alpha 1 beta-strand and alpha-helix. The effect of mutations near the peptide-binding groove suggests that bound peptides may directly or indirectly affect HLA epitopes. These results illustrate that HLA epitope conformation is very sensitive to changes at distant HLA sites and forecast that epitope models based on sequential amino acid residues will often fail to predict HLA epitopes.
我们研究了HLA - B0702 α1结构域中的突变对几种特征明确的单克隆抗体结合的影响。BB7.1识别α螺旋，对第67位残基有特殊要求。结合对α2α螺旋的既定要求，BB7.1似乎跨越了B0702肽结合槽。或者，BB7.1表位构象可能会被B0702的远端位点改变。ME1和B27M1识别连接环残基41和43以及α1α螺旋残基67 - 71。然而，ME1似乎不是直接接触残基67 - 71的侧链，而是识别一种依赖于这些HLA残基与其他残基正确相互作用的B0702构象。除了溶剂可及的残基41和43外，B27M1表位还依赖于肽结合槽底部溶剂不可及的残基32。已知MB40.2需要α2 - α3交界处附近的残基169 - 182，它还需要α1β链和α螺旋中远端残基的正确组合。肽结合槽附近突变的影响表明结合的肽可能直接或间接影响HLA表位。这些结果表明HLA表位构象对HLA远端位点的变化非常敏感，并预测基于连续氨基酸残基的表位模型通常无法预测HLA表位。
