Hillen Nina, Mester Gabor, Lemmel Claudia, Weinzierl Andreas O, Müller Margret, Wernet Dorothee, Hennenlotter Jörg, Stenzl Arnulf, Rammensee Hans-Georg, Stevanović Stefan
Department of Immunology, University of Tübingen, Tübingen, Germany.
Eur J Immunol. 2008 Nov;38(11):2993-3003. doi: 10.1002/eji.200838632.
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-B18, B37, B40, B41, B44, B45, B47, B49 and B50) 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-B44 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.
长期以来，人类白细胞抗原（HLA）被归为多个超型，以促进基于肽的免疫治疗。对HLA - B44超型的所有九种抗原（HLA - B18、B37、B40、B41、B44、B45、B47、B49和B50）所呈递的数百种肽进行分析后，发现每种抗原都有独特的肽基序。综合考虑所有超型成员，在670种天然配体中，只有25种在不止一种HLA分子上被发现。通过两种质谱方法——同位素标记以及无标记方法——进行的进一步直接比较始终表明，不同HLA抗原的配体组之间只有不到3%的微小重叠。此外，健康供体针对来自EBV的免疫显性HLA - B44和HLA - B*40表位的T细胞反应在HLA - B44超型内缺乏混杂的T细胞识别。综上所述，这些结果对该超型内广泛呈递表位的常见范式提出了挑战。
