Regulation of encephalitogenic T cells with recombinant TCR ligands

Gregory G. Burrows, Kirsten L. Adlard, Bruce F. Bebo, Justin W. Chang, Kirill Tenditnyy, Arthur Vandenbark, Halina Offner

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

We have previously described recombinant MHC class II β1 and α1 domains loaded with free antigenic peptides with potent inhibitory activity on encephalitogenic T cells. We have now produced single-chain constructs in which the peptide Ag is genetically encoded within the same exon as the linked β1 and α1 domains, overcoming the problem of displacement of peptide Ag from the peptide binding cleft. We here describe clinical effects of recombinant TCR ligands (RTLs) comprised of the rat RT1.B β1α1 domains covalently linked to the 72-89 peptide of guinea pig myelin basic protein (RTL-201), to the corresponding 72-89 peptide from rat myelin basic protein (RTL-200), or to cardiac myosin peptide CM-2 (RTL-203). Only RTL-201 possessed the ability to prevent and treat active or passive experimental autoimmune encephalomyelitis. Amelioration of experimental autoimmune encephalomyelitis was associated with a selective inhibition of proliferation response and cytokine production by Ag-stimulated lymph node T cells and a drastic reduction in the number of encephalitogenic and recruited inflammatory cells infiltrating the CNS. The exquisitely selective inhibition could be observed between molecules that differ by a single methyl group (the single amino acid residue difference between RTL-200 (threonine) and RTL-201 (serine) at position 80 of the myelin basic protein peptide). These novel RTLs provide a platform for developing potent and selective human diagnostic and therapeutic agents for treatment of autoimmune disease.

Original languageEnglish (US)
Pages (from-to)6366-6371
Number of pages6
JournalJournal of Immunology
Volume164
Issue number12
StatePublished - Jun 15 2000

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Ligands
T-Lymphocytes
Peptides
Myelin Basic Protein
Autoimmune Experimental Encephalomyelitis
Cardiac Myosins
Threonine
Serine
Autoimmune Diseases
Exons
Guinea Pigs
Lymph Nodes
Cytokines
Amino Acids

ASJC Scopus subject areas

  • Immunology

Cite this

Burrows, G. G., Adlard, K. L., Bebo, B. F., Chang, J. W., Tenditnyy, K., Vandenbark, A., & Offner, H. (2000). Regulation of encephalitogenic T cells with recombinant TCR ligands. Journal of Immunology, 164(12), 6366-6371.

Regulation of encephalitogenic T cells with recombinant TCR ligands. / Burrows, Gregory G.; Adlard, Kirsten L.; Bebo, Bruce F.; Chang, Justin W.; Tenditnyy, Kirill; Vandenbark, Arthur; Offner, Halina.

In: Journal of Immunology, Vol. 164, No. 12, 15.06.2000, p. 6366-6371.

Research output: Contribution to journalArticle

Burrows, GG, Adlard, KL, Bebo, BF, Chang, JW, Tenditnyy, K, Vandenbark, A & Offner, H 2000, 'Regulation of encephalitogenic T cells with recombinant TCR ligands', Journal of Immunology, vol. 164, no. 12, pp. 6366-6371.
Burrows GG, Adlard KL, Bebo BF, Chang JW, Tenditnyy K, Vandenbark A et al. Regulation of encephalitogenic T cells with recombinant TCR ligands. Journal of Immunology. 2000 Jun 15;164(12):6366-6371.
Burrows, Gregory G. ; Adlard, Kirsten L. ; Bebo, Bruce F. ; Chang, Justin W. ; Tenditnyy, Kirill ; Vandenbark, Arthur ; Offner, Halina. / Regulation of encephalitogenic T cells with recombinant TCR ligands. In: Journal of Immunology. 2000 ; Vol. 164, No. 12. pp. 6366-6371.
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