Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
J Immunol. 2011 May 15;186(10):5663-74. doi: 10.4049/jimmunol.1100287. Epub 2011 Apr 13.
The sequence diversity of HIV-1 presents a challenge for the development of an effective HIV-1 vaccine, because such a vaccine must confer protection against diverse forms of the virus. The present studies were initiated to explore how vaccine-induced clonal populations of CD8(+) T lymphocytes of rhesus monkeys recognize variants of an HIV-1 envelope epitope sequence. Evaluating a subset of variants of a selected epitope peptide that retain their binding to the MHC class I molecule of rhesus monkeys that presents this epitope peptide, we show that vaccine-elicited CD8(+) T lymphocytes comparably recognize the wild-type and a number of variant epitope peptides as determined by tetramer binding assays. In fact, the same clonal populations of CD8(+) T lymphocytes recognize the wild-type and variant epitope peptides. However, functional assays show that many of these variant epitope peptides stimulate suboptimal cytokine production by the vaccine-elicited CD8(+) T lymphocytes. These findings suggest that vaccine-induced CD8(+) T lymphocyte populations may recognize diverse forms of a viral epitope, but may not function optimally to confer protection against viruses expressing many of those variant sequences.
HIV-1 的序列多样性给有效的 HIV-1 疫苗的开发带来了挑战，因为这种疫苗必须能够预防多种形式的病毒。本研究旨在探索恒河猴的疫苗诱导的 CD8(+)T 淋巴细胞克隆群体如何识别 HIV-1 包膜表位序列的变体。评估与呈递该表位肽的恒河猴 MHC Ⅰ类分子结合保留的选定表位肽的一部分变体，我们通过四聚体结合测定显示，疫苗诱导的 CD8(+)T 淋巴细胞可比照识别野生型和许多变体表位肽。实际上，相同的 CD8(+)T 淋巴细胞克隆群体识别野生型和变体表位肽。然而，功能测定表明，这些变体表位肽中的许多刺激了疫苗诱导的 CD8(+)T 淋巴细胞产生次优细胞因子。这些发现表明，疫苗诱导的 CD8(+)T 淋巴细胞群体可能识别病毒表位的多种形式，但可能无法发挥最佳作用，无法预防表达许多这些变体序列的病毒。
