Essential differences in ligand presentation and T cell epitope recognition among HLA molecules of the HLA-B44 supertype
Essential differences in ligand presentation and T cell epitope recognition among HLA molecules of the HLA-B44 supertype
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DOI：
10.1002/eji.200838632
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发表时间：
2008-11-01
影响因子：
5.4
通讯作者：
Stevanovic, Stefan
中科院分区：
文献类型：
--
作者：
Hillen, Nina;Mester, Gabor;Stevanovic, Stefan
人类白细胞抗原(人类白细胞抗原)长期以来一直被划分为超类型，以促进基于多肽的免疫治疗。对人类白细胞抗原B*18、B*37、B*40、B*41、B*44、B*45、B*47、B*49和B*50这9种超型抗原所呈现的数百种多肽进行了分析，发现每一种多肽都具有独特的多肽基序。考虑到所有超型成员，在670个自然配体中只有25个存在于一个以上的HLA分子上。进一步通过两种质谱学方法--同位素标记和无标记方法--的进一步直接比较，一致地表明不同的人类白细胞抗原的配基之间只有不到3%的微小重叠。此外，健康献血者对EBV免疫优势的HLA-B*44和HLA-B*40表位的T细胞反应缺乏对HLA-B44超型的混杂T细胞识别。综上所述，这些结果挑战了这种超类型中广泛呈现的表位的常见范式。
Human leukocyte antigens (HLA) have long been grouped into supertypes to facilitate peptide-based immunotherapy. Analysis of several hundreds of peptides presented by all nine antigens of the HLA-B44 supertype (HLA-B*18, B*37, B*40, B*41, B*44, B*45, B*47, B*49 and B*50) revealed unique peptide motifs for each of them. Taking all supertype members into consideration only 25 out of 670 natural ligands were found on more than one HLA molecule. Further direct comparisons by two mass spectrometric methods - isotope labeling as well as a label-free approach - consistently demonstrated only minute overlaps of below 3% between the ligandomes of different HLA antigens. In addition, T cell reactions of healthy donors against immunodominant HLA-B*44 and HLA-B*40 epitopes from EBV lacked promiscuous T-cell recognition within the HLA-B44 supertype. Taken together, these results challenge the common paradigm of broadly presented epitopes within this supertype.