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La Jolla Institute scientist identifies previously unknown T cell interaction

August 25, 2017

Dr. Rudd added that the finding brings the work of Dr. Altman full circle. "Many people discover something and then other scientists build on their discovery," said Dr. Rudd. "In Dr. Altman's case, not only was he the first to discover the PKC-?? enzyme, which served as an important tool for numerous groups around the world, but he has now discovered a new mechanism by which PKC-?? regulates immune function. He's drawn a circle around his initial discovery by outlining its importance and how it works. This will have an important impact on the field of immunology."

Dr. Altman said efforts to develop small molecule drugs to block the PKC-?? enzyme's activity have been ongoing at several drug companies based on the previous knowledge of the enzyme's importance in T cell activation. "Here, we have found an alternative way of blocking the function of PKC-??, not by inhibiting its enzymatic activity, but by inhibiting its recruitment to the immunological synapse, which is that part of the cell where it needs to be to activate T cells," he said. "Essentially, the enzyme remains fully active, but it can't trigger T cell activation because it's not in the right place in the cell."

Dr. Altman said that targeting the interaction between PKC-?? and CD28 in T cells is likely to be highly selective and, therefore, have minimal undesirable side effects on other cells and tissues because "T cells are the only cell type where the PKC-?? enzyme and CD28 are expressed together."

He noted, however, that creating a way to therapeutically block the binding of PKC-?? to CD28 is not an easy task, and will require creative strategies and diligence. "Several possibilities exist, such as using a peptide to block the interaction. However, getting a peptide into a T cell is not a trivial matter," said Dr. Altman. "While we consider our finding very promising, we know that developing a therapeutic to block this interaction is not something that will happen next year. It will take time, but the potential is exciting."

Source: La Jolla Institute