Purbhoo M A, Sewell A K, Klenerman P, Goulder P J, Hilyard K L, Bell J I, Jakobsen B K, Phillips R E
University of Oxford, Nuffield Department of Medicine and Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4527-32. doi: 10.1073/pnas.95.8.4527.
It is not known how human immunodeficiency virus type 1 (HIV-1)-derived antagonist peptides interfere with intracellular activation of cytotoxic T lymphocytes (CTL). We identified Gag epitope variants in HIV-1-infected patients that act as antagonists of CTL responses to unmutated epitopes. We then investigated the effect that presentation of each variant has on the early events of T cell receptor (TCR) signal transduction. We found that altered peptide ligands (APL) failed to induce phosphorylation of pp36, a crucial adaptor protein involved in TCR signal transduction. We further investigated the effect that simultaneous presentation of APL and native antigen at low, physiological, peptide concentrations (1 nM) has on TCR signal transduction, and we found that the presence of APL can completely inhibit induction of the protein tyrosine phosphorylation events of the TCR signal transduction cascade.
目前尚不清楚1型人类免疫缺陷病毒（HIV-1）衍生的拮抗肽如何干扰细胞毒性T淋巴细胞（CTL）的细胞内激活。我们在HIV-1感染患者中鉴定出了Gag表位变体，这些变体可作为CTL对未突变表位反应的拮抗剂。然后，我们研究了每个变体的呈递对T细胞受体（TCR）信号转导早期事件的影响。我们发现，改变的肽配体（APL）未能诱导pp36的磷酸化，pp36是参与TCR信号转导的关键衔接蛋白。我们进一步研究了在低生理肽浓度（1 nM）下同时呈递APL和天然抗原对TCR信号转导的影响，我们发现APL的存在可完全抑制TCR信号转导级联的蛋白酪氨酸磷酸化事件的诱导。
