Morio T, Chatila T, Geha R S
Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Int Immunol. 1997 Jan;9(1):53-64. doi: 10.1093/intimm/9.1.53.
HIV major glycoprotein gp120 interacts with CD4 molecules and perturbs signaling through the TCR-CD3 complex. We examined the effects of gp120 on TCR-CD3-induced phosphorylation and activation of the src-type protein tyrosine kinases (PTK), fyn and lck. gp120 caused minimal changes in lck phosphorylation or lck enzymatic activity, but preincubation of Jurkat cells with gp120 for 20 min strongly inhibited TCR-CD3-mediated phosphorylation and activation of lck and fyn, as well as phosphorylation of CD3 zeta. Inhibition of TCR-CD3 signaling in T cells preincubated with gp120 was paralleled by inhibition of T cell proliferation to the antigen tetanus toxoid. Neither surface CD4 expression nor CD4-lck association was affected by gp120. Furthermore, gp120 inhibited lck phosphorylation induced by cross-linking of TCR-CD3 and CD4 suggesting that the inhibition of lck phosphorylation could not be simply accounted for by sequestration of CD4 molecules. gp120 selectively enhanced the phosphorylation of the lck peptide containing the autoinhibitory tyrosine residue Tyr505 relative to the lck peptide containing the positive regulatory residue Tyr394, suggesting that a qualitative alteration in lck may underlie the inhibition of TCR-CD3 signaling by gp120.
人类免疫缺陷病毒主要糖蛋白gp120与CD4分子相互作用，并通过TCR-CD3复合体干扰信号传导。我们研究了gp120对TCR-CD3诱导的src型蛋白酪氨酸激酶（PTK）fyn和lck磷酸化及激活的影响。gp120对lck磷酸化或lck酶活性的影响极小，但将Jurkat细胞与gp120预孵育20分钟可强烈抑制TCR-CD3介导的lck和fyn磷酸化及激活，以及CD3 ζ链的磷酸化。用gp120预孵育的T细胞中TCR-CD3信号传导的抑制与T细胞对抗原破伤风类毒素的增殖抑制并行。gp120既不影响表面CD4表达，也不影响CD4与lck的结合。此外，gp120抑制了TCR-CD3和CD4交联诱导的lck磷酸化，这表明lck磷酸化的抑制不能简单地用CD4分子的隔离来解释。相对于含有正调节性残基Tyr394的lck肽段，gp120选择性地增强了含有自身抑制性酪氨酸残基Tyr505的lck肽段的磷酸化，这表明lck的定性改变可能是gp120抑制TCR-CD3信号传导的基础。
