Several HLA alleles share overlapping peptide specificities.
Several HLA alleles share overlapping peptide specificities.
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DOI：
10.4049/jimmunol.154.1.247
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发表时间：
1995-01
影响因子：
4.4
通讯作者：
J. Sidney;M. D. Guercio;S. Southwood;V. Engelhard;E. Appella;H. Rammensee;K. Falk;O. Rötzschke;M. Takiguchi;R. Kubo
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文献类型：
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作者：
J. Sidney;M. D. Guercio;S. Southwood;V. Engelhard;E. Appella;H. Rammensee;K. Falk;O. Rötzschke;M. Takiguchi;R. Kubo
在此，我们描述了测定肽与纯化的HLA-B *0701、-B*0801、-B*2705、-B*3501-03、-B*5401、-Cw*0401、-Cw*0602和-Cw*0702分子结合的测定法的建立。已知肽表位或天然加工肽的结合与HLA限制性或起源密切相关，强调了这些测定的免疫学相关性。各种HLA I类等位基因的序列分析表明，具有以2位脯氨酸和C端芳香或疏水残基为特征的肽基序的等位基因在9、63、66、67和70位（B口袋）和残基116（F口袋）共享关键的共有残基。基于这种共有的B和F口袋结构，对HLA-B*5401的肽结合特异性的预测证实了这一假设，并表明一个相对较大的HLA-B等位基因家族（我们将其定义为HLA-B7样超型）可能在肽结合特异性方面显著重叠。定量结合试验的可用性允许验证，事实上，许多（25%）的肽配体携带脯氨酸在位置2和疏水/芳香族残基在C-末端（B7样超基序）能够结合至少三个5 HLA-B7样超型等位基因。鉴定携带B7样超基序并与来自所有主要种族群体的超过40%的个体中代表的等位基因家族结合的表位在肽疫苗的设计中可能具有相当大的用途。
Herein we describe the establishment of assays to measure peptide binding to purified HLA-B*0701, -B*0801, -B*2705, -B*3501-03, -B*5401, -Cw*0401, -Cw*0602, and -Cw*0702 molecules. The binding of known peptide epitopes or naturally processed peptides correlates well with HLA restriction or origin, underscoring the immunologic relevance of these assays. Analysis of the sequences of various HLA class I alleles suggested that alleles with peptide motifs characterized by proline in position 2 and aromatic or hydrophobic residues at their C-terminus shared key consensus residues at positions 9, 63, 66, 67, and 70 (B pocket) and residue 116 (F pocket). Prediction of the peptide-binding specificity of HLA-B*5401, on the basis of this consensus B and F pocket structure, verified this hypothesis and suggested that a relatively large family of HLA-B alleles (which we have defined as the HLA-B7-like supertype) may significantly overlap in peptide binding specificity. Availability of quantitative binding assays allowed verification that, indeed, many (25%) of the peptide ligands carrying proline in position 2 and hydrophobic/aromatic residues at the C-terminus (the B7-like supermotif) were capable of binding at least three of five HLA-B7-like supertype alleles. Identification of epitopes carrying the B7-like supermotif and binding to a family of alleles represented in over 40% of individuals from all major ethnic groups may be of considerable use in the design of peptide vaccines.