Antigenic ligand density modulates execution of naïve CD8+ T cell response programme (110.1)

Abstract

Abstract Upon brief exposure to antigenic stimulation, naïve CD8+ T lymphocytes execute an autonomous programme of several rounds of proliferation and maturation into effector cytotoxic cells. We have studied the role of ligand density as a modifier of this program using T cell receptor (TCR)-transgenic CD8+ T cell activation by short-duration stimulation in vitro. Over the entire ligand density range studied, we observe a graded increase in the frequency of responder naïve T cells that upregulate the expression of CD69, an early activation marker. However, the levels of induced CD69 are similar at all ligand densities. When CD69+ T cells are purified at early stages and cultured, most undergo successive proliferation cycles, showing that the execution of the autonomous programme during CD8+ T cell response is independent of ligand density. However, at very low ligand densities, the efficiency with which CD69+ T cells enter proliferation is poor and slow, leading to lower cell yields. At these ligand densities, post-activation TCR internalization is also inefficient. At any given ligand density, if activated CD69+ T cells that have internalised TCR are separated from those that have not internalised TCR, TCR-high cells show a lag in proliferation regardless of the ligand density. Together, these data indicate that ligand density quantitatively modulates the lag phase of the autonomous proliferation-differentiation programme of CD8+ T cells via TCR internalization-dependent mechanism.