Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor
Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor
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DOI：
10.1073/pnas.2131705100
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发表时间：
2003-10-28
影响因子：
11.1
通讯作者：
Corey, L
中科院分区：
文献类型：
--
作者：
Koelle, DM;Liu, Z;Corey, L
微生物特异性CD 8 T细胞应答中的免疫优势研究一直具有挑战性。我们使用了一种以前未描述的方法来创建CD 8细胞毒性T淋巴细胞克隆特异性单纯疱疹病毒2型，一个复杂的基因组编码至少85个多肽的病原体无偏倚面板。循环单纯疱疹病毒2型特异性细胞富集和克隆后，分选皮肤归巢相关受体，皮肤淋巴细胞相关抗原的表达，绕过抗原再刺激。测定所得细胞毒性克隆的特异性。克隆频率进行了比较，彼此和细胞毒性克隆的总数。对于归巢受体阳性隔室内的每个受试者，CD 8细胞毒性应答由仅对少数肽特异性的T细胞主导。以前未描述的抗原和抗原决定簇在病毒被膜，衣壳，或支架蛋白免疫显性在一些科目。通过使用单纯疱疹突变体、牛痘重组体和/或酶联免疫斑点，在一些进行优势研究的受试者中证实了克隆计数分析。我们得出结论，在表达归巢相关受体的循环细胞中，在慢性疱疹2型感染期间，尽管存在许多潜在的抗原肽，但CD 8 T细胞反应变得相当集中。
The study of immunodominance within microbe-specific CD8 T cell responses has been challenging. We used a previously undescribed approach to create unbiased panels of CD8 cytotoxic T lymphocyte clones specific for herpes simplex virus type 2, a pathogen with a complex genome encoding at least 85 polypeptides. Circulating herpes simplex virus type 2-specific cells were enriched and cloned after sorting for expression of the skin homing-associated receptor, cutaneous lymphocyte-associated antigen, bypassing restimulation with antigen. The specificity of the resultant cytotoxic clones was determined. Clonal frequencies were compared with each other and with the total number of cytotoxic clones. For each subject within the homing receptor-positive compartment, the CD8 cytotoxic response was dominated by T cells specific for only a few peptides. Previously undescribed antigens and epitopes in viral tegument, capsid, or scaffold proteins were immunodominant in some subjects. Clone enumeration analyses were confirmed in some subjects with dominance studies by using herpes simplex mutants, vaccinia recombinants, and/or enzyme-linked immune spots. We conclude that among circulating cells expressing a homing-associated receptor, during chronic herpes type 2 infection, the CD8 T cell response becomes quite focused despite the presence of many potential antigenic peptides.