PLP (139-151)

• Modeling Mechanism：

  Transgenic mice with the PLP 139-151 epitope-specific T-cell receptor (TCR) exhibit peripheral CD4⁺ T cells that recognize the PLP-139-151/I-Aᵏ complex in the myelin sheath of the central nervous system (CNS). Without thymic tolerance deletion, these cells spontaneously or through induction activate and infiltrate the CNS, releasing Th1 cytokines such as IFN-γ, triggering inflammatory infiltration and demyelination damage, leading to acute exacerbation encephalitis (EAE). Non-encephalogenic TCRs (4E3 clones) exhibit a higher frequency of spontaneous disease due to their higher affinity for PLP-139-151/I-Aᵏ.

• Related Products：

  PLP (139-151) (TP1282)

• Modeling Method：

  Experimental Subject：

  Mice: SJL/J (H-2ˢ background), FVB/N (transgenic founder background), RAG-2 deficient SJL/J; 6–8 weeks of age

  Dosage and Administration Route：

  ① Spontaneous model: No administration; natural onset in SPF/VAF environment;
  ② Induced model: 25 μg PLP-139-151 peptide emulsified in complete Freund's adjuvant (CFA) containing 400 μg Mycobacterium tuberculosis, administered subcutaneously; 75 ng pertussis toxin (PT), administered intravenously;
  ③ PT-only induction: intravenous injection of 75 ng PT alone

  Dosing Frequency and Duration Model：

  In the induced model, PLP/CFA+PT was injected on day 0, with PT repeated on day 2; in the PT-only group, PT was injected once on days 0 and 2

• Validation：

  Clinical phenotype: A 0-5 scoring system was used (0 = no disease, 1 = tail weakness, 2 = gait abnormality/impaired righting reflex, 3 = complete hind limb paralysis, 4 = quadriplegia, 5 = near death); the spontaneous morbidity rate in 5B6 TCR transgenic mice was 40% (N₂-N₆ generation), while the morbidity rate in 4E3 TCR transgenic mice reached 60%-83% (N₃-N₅ generation); the induced morbidity rate was 7/7 (PLP/CFA+PT) and 5/6 (PT alone), with the onset of disease occurring earlier in 5B6 transgenic mice than in non-transgenic mice (7.2 days vs. 14.5 days); Histological markers: Numerous inflammatory foci were observed in the CNS (brain and spinal cord), with CD4⁺Vβ6⁺ T cell infiltration being the predominant feature in 5B6 transgenic mice, while no inflammation was observed in non-transgenic mice; Molecular markers: Splenic cells proliferated rapidly after stimulation with PLP-139-151, secreting large amounts of IFN-γ. Released IL-2, but no IL-4/IL-10/TNF-α; flow cytometry detected high expression of transgenic Vβ6 in peripheral CD4⁺ T cells (5B6 mice > 98%).

*Precautions： Brain and spinal cord tissues were collected from all mice at the time of sacrifice and fixed in 10% formalin or OCT and frozen.

*References：Waldner H,et,al. Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3412-7.