J Exp Med 1999 Apr 19;189(8):1275-84
Microbial epitopes act as altered peptide ligands to prevent experimental
autoimmune encephalomyelitis.
Ruiz PJ, Garren H, Hirschberg DL, Langer-Gould AM, Levite M, Karpuj MV, Southwood S, Sette A, Conlon P,
Steinman L
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305,
USA.
[Medline record in process]
Molecular mimicry refers to structural homologies between a self-protein and a microbial protein. A major epitope of myelin
basic protein (MBP), p87-99 (VHFFKNIVTPRTP), induces experimental autoimmune encephalomyelitis (EAE). VHFFK
contains the major residues for binding of this self-molecule to T cell receptor (TCR) and to the major histocompatibility
complex. Peptides from papilloma virus strains containing the motif VHFFK induce EAE. A peptide from human papilloma
virus type 40 (HPV 40) containing VHFFR, and one from HPV 32 containing VHFFH, prevented EAE. A sequence from
Bacillus subtilis (RKVVTDFFKNIPQRI) also prevented EAE. T cell lines, producing IL-4 and specific for these microbial
peptides, suppressed EAE. Thus, microbial peptides, differing from the core motif of the self-antigen, MBPp87-99, function as
altered peptide ligands, and behave as TCR antagonists, in the modulation of autoimmune disease.
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