Sidney J, Southwood S, Mann D L, Fernandez-Vina M A, Newman M J, Sette A
Epimmune, Inc., San Diego, CA 92121, USA.
Hum Immunol. 2001 Nov;62(11):1200-16. doi: 10.1016/s0198-8859(01)00319-6.
The A0201, A 0202, A0203, A0206, and A*6802 binding capacity of single amino acid substitution analogs of known A2-supertype binding peptides and of large nonredundant peptide libraries was measured. The results were utilized to rigorously define the peptide binding specificities of these A2-supertype molecules. Although each molecule was noted to have unique preferences, large overlaps in specificity were found. The presence of L, I, V, M, A, T, and Q residues in position 2, and L, I, V, M, A, and T residues at the C-terminus of peptide ligands were tolerated by all molecules. Likewise, whereas examination of secondary influences on peptide binding revealed allele specific preferences, shared features could also be identified. These shared features were utilized to define an A2-supermotif and were noted to correlate with crossreactivity. Over 70% of the peptides that bound A *0201 with high affinity were found to bind at least two other A2-supertype molecules. Because the A2-supertype molecules studied herein cover the variants most common in different major ethnicities, these findings have important implications for epitope-based approaches to vaccination, immunotherapy, and the monitoring of immune responses.
测定了已知A2超型结合肽的单氨基酸取代类似物以及大型非冗余肽库与A0201、A0202、A0203、A0206和A6802的结合能力。利用这些结果严格定义了这些A2超型分子的肽结合特异性。尽管注意到每个分子都有独特的偏好，但在特异性方面发现了很大的重叠。肽配体第2位存在L、I、V、M、A、T和Q残基，以及肽配体C端存在L、I、V、M、A和T残基，所有分子均可耐受。同样，虽然对肽结合的二级影响的研究揭示了等位基因特异性偏好，但也可以识别出共同特征。这些共同特征被用于定义一个A2超基序，并被指出与交叉反应性相关。发现与A0201高亲和力结合的肽中，超过70%至少能与其他两种A2超型分子结合。由于本文研究的A2超型分子涵盖了不同主要种族中最常见的变体，这些发现对基于表位的疫苗接种、免疫治疗和免疫反应监测方法具有重要意义。
