Weaker is better
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《细胞学杂志》
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 contrast, selectively eliminated the most menacing of IGRP-reactive T cells, while maintaining a substantial population of more benign T cells that recognized, but were not harmed by, the peptides. By becoming established as the dominant population, the nonpathogenic T cells effectively blocked more reactive but less prevalent T cells from taking over.
Now with a better grasp on the fine balance between ligand binding and dosage, Santamaria says, "targeting multiple epitopes simultaneously is likely to be more practical than finding the optimal dose for deletion of high-avidity subtypes while preserving low-avidity subtypes."
Reference:
Han, B., et al. 2005. Nat. Med. doi:10.1038/nm1250.(Antigenic therapy researchers have long )
Low-affinity peptides, by contrast, selectively eliminated the most menacing of IGRP-reactive T cells, while maintaining a substantial population of more benign T cells that recognized, but were not harmed by, the peptides. By becoming established as the dominant population, the nonpathogenic T cells effectively blocked more reactive but less prevalent T cells from taking over.
Now with a better grasp on the fine balance between ligand binding and dosage, Santamaria says, "targeting multiple epitopes simultaneously is likely to be more practical than finding the optimal dose for deletion of high-avidity subtypes while preserving low-avidity subtypes."
Reference:
Han, B., et al. 2005. Nat. Med. doi:10.1038/nm1250.(Antigenic therapy researchers have long )