PLP 139-151 is the immunodominant encephalitogenic epitope of myelin proteolipid protein in SJL/J mice and the standard antigen for inducing relapsing experimental autoimmune encephalomyelitis. This product substitutes alanine for the native tryptophan at position 144, the sixth residue of the supplied sequence. Position 144 is the principal T-cell receptor contact of this epitope, which is why it is the position most often altered when building analogues. Alanine substitution is the most conservative probe available: replacing a large indole side chain with a methyl group removes the contact almost entirely while leaving backbone geometry and MHC anchoring largely intact. In practice this makes an alanine analogue at a primary TCR contact the closest thing to a null ligand in the series, and it is used to establish how much of a response depends on that single residue. Fine-specificity mapping of CD4+ T-cell responses to this epitope in SJL/J mice showed that the responding repertoire is not uniform, and different clones within it tolerate substitution differently. An alanine analogue can therefore reduce a polyclonal response without abolishing it, which is informative rather than a failure of the reagent. Determine the behaviour of this analogue in your own system: within this series, substitutions can yield partial agonists, null ligands or antagonists, and the outcome depends on the responding clone. | 