[Leu144, Arg147] - PLP (139 - 151), [L144, R147 - PLP(139 - 151)

This is the double-substituted analogue of PLP 139-151, carrying leucine at position 144 in place of the native tryptophan and arginine at position 147 in place of histidine. Both changes are visible in the supplied sequence, and it is the best characterised altered peptide ligand derived from this epitope.

Its significance is that it behaves as a T-cell receptor antagonist rather than a weak agonist. Work published in PNAS reported that a receptor antagonist peptide from this epitope induces T cells capable of bystander suppression, preventing autoimmune encephalomyelitis induced not only by PLP but by multiple myelin antigens. That is a mechanistically different result from simply failing to activate: the analogue elicits a regulatory population that acts on responses to unrelated antigens, which is why this peptide became a reference compound for antigen-specific immunotherapy rather than only a specificity control.

The two substitutions are not redundant. Position 144 is the dominant receptor contact and 147 a secondary one, and the antagonist phenotype is associated with the combination. For experiments intended to separate their contributions, the single-substitution leucine-144 analogue (LT0629) is the appropriate comparator. Antagonist activity is receptor-dependent, so confirm the effect on the clones or polyclonal population in use rather than assuming it transfers.

• T-cell receptor antagonism and altered peptide ligand studies
• Bystander suppression and regulatory T-cell induction experiments
• EAE prevention and antigen-specific immunotherapy models
• Paired with the single-substitution analogue to separate position contributions
• MHC class II binding and competition assays

1. A T cell receptor antagonist peptide induces T cells that mediate bystander suppression and prevent autoimmune encephalomyelitis induced with multiple myelin antigens. PNAS (1997) 94:9279. doi:10.1073/pnas.94.17.9279

2. On peptides and altered peptide ligands: from origin, mode of action and design to clinical application (immunotherapy). PMC7058415

3. Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein. (1992). PMID 1376328

4. Fine specificity of CD4+ T cell responses to the dominant encephalitogenic PLP 139-151 peptide in SJL/J mice. (1994). PMID 7528357