Antigenic therapy researchers have long relied on repeated dosing of high-affinity ligands to inactivate select T cells by causing overstimulation that leads to apoptosis. Contrary to this strategy, Bingye Han, Pau Serra, Pere Santamaria (University of Calgary, Alberta, Canada), and colleagues now show that low-affinity peptides targeting autoreactive T cells protect mice more effectively against diabetes than do high-affinity peptides.
Peptides that are similar in sequence to a portion of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that strongly bound to autoreactive T cells nearly completely obliterated this T cell pool in mice. But lurking in the background were smaller pools of autoreactive T cells that were impervious to the high-affinity peptide, yet reactive against other portions of IGRP. Once their competition had been eliminated, these cells emerged to fill in the vacant niche. The high-affinity peptide thus failed to protect against diabetes.
Low-affinity peptides, by...
