Brookes R, Bergmeier L A, Mitchell E, Walker J, Tao L, Klavinskis L, Meyers N J, Layton G, Adams S E, Lehner T
Department of Immunology, United Medical School, Guy's & St Thomas' Hospital, London, UK.
AIDS. 1995 Sep;9(9):1017-24. doi: 10.1097/00002030-199509000-00006.
To examine whether the route of immunization determines the hierarchy of T-cell epitope proliferative responses in macaques.
Macaques were immunized with a recombinant simian immunodeficiency virus (SIV) p27 core protein by the intramuscular, male and female genital or rectal route, each of which was augmented by oral immunization, and by the novel targeted lymph-node immunization route. Overlapping peptides were used to identify the proliferative T-cell epitopes and to determine their hierarchy in the circulation, spleen and lymph nodes.
T-cell epitope mapping of the proliferative responses was studied in short-term cell lines. Dendritic cells and macrophages were enriched by metrizamide gradient and adherence to plastic, respectively.
Intramuscular immunization elicited in the circulating T cells a hierarchy of T-cell epitopes within four peptides in the following descending order of frequency: peptides 121-140 (57.9%), 41-60 (28.9%), 61-80 (18.9%) and 101-120 (5.4%). The hierarchy of these four T-cell epitope responses differed significantly with each of the five routes of immunization, when circulating (P < 0.001), splenic (P < 0.02-< 0.001) or iliac lymph-node cells (P < 0.001) were analysed. The effect of antigen-presenting cells was then investigated and enriched dendritic cells were more effective than macrophages in processing and presenting the p27 antigen and the immunodominant (121-140) and 61-80 T-cell epitopes.
The route of immunization may determine the hierarchy of T-cell epitopes in the lymph nodes draining the mucosa in the circulating and splenic lymphocytes. The diversity of T-cell epitopes may affect the control of HIV at different anatomical sites, the administration route of the vaccine, and selection of polypeptides or recombinant antigens for immunization.
研究免疫途径是否决定猕猴体内T细胞表位增殖反应的层次结构。
用重组猿猴免疫缺陷病毒（SIV）p27核心蛋白通过肌肉注射、男性和女性生殖器或直肠途径对猕猴进行免疫，每种途径均通过口服免疫增强，并采用新型靶向淋巴结免疫途径。使用重叠肽来鉴定增殖性T细胞表位，并确定它们在循环系统、脾脏和淋巴结中的层次结构。
在短期细胞系中研究增殖反应的T细胞表位图谱。分别通过密度梯度离心和贴壁法富集树突状细胞和巨噬细胞。
肌肉注射在循环T细胞中引发了四个肽段内T细胞表位的层次结构，频率由高到低依次为：肽段121 - 140（57.9%）、41 - 60（28.9%）、61 - 80（18.9%）和101 - 120（5.4%）。当分析循环（P < 0.001）、脾脏（P < 0.02 - < 0.001）或髂淋巴结细胞（P < 0.001）时，这四种T细胞表位反应的层次结构在五种免疫途径中的每一种之间均存在显著差异。然后研究了抗原呈递细胞的作用，富集的树突状细胞在处理和呈递p27抗原以及免疫显性（121 - 140）和61 - 80 T细胞表位方面比巨噬细胞更有效。
免疫途径可能决定循环和脾脏淋巴细胞中引流黏膜的淋巴结内T细胞表位的层次结构。T细胞表位的多样性可能会影响不同解剖部位对HIV的控制、疫苗的给药途径以及用于免疫的多肽或重组抗原的选择。
