PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1.

The programmed death-1 (PD-1) molecule is involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. PD-1 interacts with two ligands, PD-L1 and PD-L2. We have investigated the molecular mechanisms of PD-1 interactions with its ligands by surface plasmon resonance and cell surface binding as well as the ability of the two ligands to compete for PD-1 binding.

Dok-4 is a novel negative regulator of T cell activation.

Dok-4 (downstream of tyrosine kinase-4) is a recently identified member of the Dok family of adaptor proteins, which are characterized by an amino-terminal pleckstrin homology domain, a phosphotyrosine-binding domain, and a carboxyl-terminal region containing several tyrosines and poly-proline-rich motifs. Two members of the Dok family, Dok-1 and Dok-2, have already been described as negative regulators in T cells. However, the function of Dok-4, which is also expressed in T cells, remains unknown.

ICOS ligation recruits the p50alpha PI3K regulatory subunit to the immunological synapse.

ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85alpha subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling. However, ICOS costimulation shows greater PI3K activity than CD28 in T cells.

The SH3 domain of Tec kinase is essential for its targeting to activated CD28 costimulatory molecule.

The Tec family of protein tyrosine kinases plays an important role in T cell signaling. Tec, the prototypical member of this kinase family, can interact with CD28, which is a costimulatory molecule. However, the regulation of Tec upon CD28 stimulation remains poorly understood.