Palmitoylation of CD44 interferes with CD3-mediated signaling in human T lymphocytes.

We studied the interactions between CD44 and four different monoclonal anti-CD44 antibodies. All four monoclonal anti-CD44 antibodies studied (P3H9, Bu52, IM.7, and GKW.A3) act in synergy with human anti-CD2 antibodies in stimulating normal human peripheral blood lymphocytes to proliferate. GKW.A3 and IM.7 but not P3H9 or Bu52 inhibited the proliferation of normal human peripheral blood lymphocytes stimulated by anti-CD3. Interestingly, only GKW.A3 and IM.7 stimulated the incorporation of [3H]palmitic acid and palmitoylation of CD44 molecules by normal human peripheral blood lymphocytes. The two monoclonal anti-CD44 antibodies (P3H9 and Bu52) that failed to inhibit anti-CD3 induced proliferation also failed to induce the incorporation of [3H]palmitic acid. More importantly, the inhibitory effects of GKW.A3 were reversed in the presence of cerulenin, an inhibitor of protein palmitoylation. Therefore, palmitoylation of CD44 may interfere with anti-CD3 mediated signaling pathways. These data support the hypothesis that palmitoylation of cell surface receptors may play an active role in receptor and receptor interactions and signal transduction in normal human T lymphocytes.