Immunology
A Molecular Switch Abrogates Glycoprotein 100 (gp100) T-cell Receptor (TCR) Targeting of a Human Melanoma Antigen
Human CD8+ cytotoxic T lymphocytes can mediate tumor regression in melanoma through the specific recognition of HLA-restricted peptides. Because of the relatively weak affinity of most anti-cancer T-cell receptors (TCRs), there is growing emphasis on immunizing melanoma patients with altered peptide ligands in order to induce strong anti-tumor immunity capable of breaking tolerance toward these self-antigens. However, previous studies have shown that these immunogenic designer peptides are not always effective.Distortion of the Major Histocompatibility Complex Class I Binding Groove to Accommodate an Insulin-derived 10-Mer Peptide
Background CD8+ T-cells play a central role in type 1 diabetes (T1D) by recognizing insulin peptides displayed by MHC. Results A novel flexible MHC binding mode accommodates extra C-terminal peptide residues. Conclusion Unusual peptide-MHC binding might explain weak TCR affinity of a natural T1D epitope. Significance MHC peptide binding can be highly flexible around the F-binding pocket.
