Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nat Med. 2010 Nov;16(11):1333-40. doi: 10.1038/nm.2248. Epub 2010 Oct 31.
Immunodominance is defined as restricted responsiveness of T cells to a few selected epitopes from complex antigens. Strategies currently used for elucidating CD4(+) T cell epitopes are inadequate. To understand the mechanism of epitope selection for helper T cells, we established a cell-free antigen processing system composed of defined proteins: human leukocyte antigen-DR1 (HLA-DR1), HLA-DM and cathepsins. Our reductionist system successfully identified the physiologically selected immunodominant epitopes of two model antigens: hemagglutinin-1 (HA1) from influenza virus (A/Texas/1/77) and type II collagen (CII). When applied for identification of new epitopes from a recombinant liver-stage antigen of malaria falciparum (LSA-NRC) or HA1 from H5N1 influenza virus ('avian flu'), the system selected single epitopes from each protein that were confirmed to be immunodominant by their capacity to activate CD4(+) T cells from H5N1-immunized HLA-DR1-transgenic mice and LSA-NRC-vaccinated HLA-DR1-positive human volunteers. Thus, we provide a new tool for the identification of physiologically relevant helper T cell epitopes from antigens.
免疫优势是指 T 细胞对复杂抗原中少数几个选定表位的受限反应性。目前用于阐明 CD4(+) T 细胞表位的策略并不充分。为了了解辅助性 T 细胞表位选择的机制，我们建立了一个由定义明确的蛋白质组成的无细胞抗原处理系统：人白细胞抗原-DR1（HLA-DR1）、HLA-DM 和组织蛋白酶。我们的简化系统成功地鉴定了两种模型抗原的生理性选择的免疫优势表位：流感病毒（A/Texas/1/77）的血凝素-1（HA1）和 II 型胶原（CII）。当应用于鉴定疟原虫裂殖体阶段抗原（LSA-NRC）或 H5N1 流感病毒（“禽流感”）HA1 的新表位时，该系统从每个蛋白中选择了单一表位，这些表位被证明能够激活来自 H5N1 免疫 HLA-DR1 转基因小鼠和 LSA-NRC 疫苗接种 HLA-DR1 阳性人类志愿者的 CD4(+) T 细胞，因此具有免疫优势。因此，我们提供了一种从抗原中鉴定生理相关辅助性 T 细胞表位的新工具。
