Malignant Haematology and Stem Cell Transplantation Service, The Alfred Hospital, Victoria, Australia.
Immunol Cell Biol. 2010 Aug;88(6):676-84. doi: 10.1038/icb.2010.20. Epub 2010 Mar 2.
CD8(+) T cell immunity has a critical function in controlling human cytomegalovirus (HCMV) infection. In immunocompromized individuals, HCMV reactivation or disease can lead to increased morbidity and mortality, particularly in transplant recipients. In this setting, adoptive transfer of HCMV-specific CD8(+) T cells is a promising vaccine strategy to restore viral immunity, with most clinical approaches focussing on the use of peptides for the generation of single epitope-specific CD8(+) T cells. We show that using an IE1-pp65 chimeric protein as the antigen source promotes effective cross-presentation, by monocyte-derived dendritic cells (MoDCs), to generate polyclonal CD8(+) T cell epitopes. By exploring human leukocyte antigen (HLA)-restricted immunodominance hierarchies both within and across two immunodominant proteins, we show that HLA-B7 epitopes elicit higher CD8(+) T cell responses compared with HLA-A1, -A2 or -B8. This study provides important evidence highlighting both the efficacy of the IE1-pp65 chimeric protein and the importance of immunodominance in designing future therapeutic vaccines.
CD8(+) T 细胞免疫在控制人类巨细胞病毒（HCMV）感染中具有关键作用。在免疫功能低下的个体中，HCMV 的再激活或疾病可导致发病率和死亡率增加，特别是在移植受者中。在这种情况下，过继转移 HCMV 特异性 CD8(+) T 细胞是一种有前途的疫苗策略，可以恢复病毒免疫力，大多数临床方法都集中在使用肽来产生单一表位特异性 CD8(+) T 细胞。我们表明，使用 IE1-pp65 嵌合蛋白作为抗原来源可通过单核细胞衍生的树突状细胞（MoDC）促进有效的交叉呈递，从而产生多克隆 CD8(+) T 细胞表位。通过探索两个免疫显性蛋白内和跨内的 HLA 限制性免疫优势层次结构，我们表明与 HLA-A1、A2 或 B8 相比，HLA-B7 表位引发更高的 CD8(+) T 细胞反应。这项研究提供了重要证据，突出了 IE1-pp65 嵌合蛋白的功效以及设计未来治疗性疫苗时免疫优势的重要性。
