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The crystal structures of three TCRs that ranged from highly crossreactive to largely noncrossreactive were determined. The authors showed that crossreactivity correlated with a shrinking, increasingly hydrophobic TCR-ligand interface, involving fewer TCR amino acids.
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Dai S., Huseby E.S., Rubtsova K., Scott-Browne J., Crawford F., Macdonald W.A., Marrack P., and Kappler J.W. Crossreactive T cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules. Immunity 28 (2008) 324-334. The crystal structures of three TCRs that ranged from highly crossreactive to largely noncrossreactive were determined. The authors showed that crossreactivity correlated with a shrinking, increasingly hydrophobic TCR-ligand interface, involving fewer TCR amino acids.
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This study showed that a naturally processed bacterial peptide could structurally mimic MBP in its interaction with Ob.1A12 TCR, and that this crossreactivity induced an MS-like disease in humanized mice.
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