Identification and characterization of a second encephalitogenic determinant of myelin proteolipid protein (residues 178-191) for SJL mice.
We previously described a synthetic peptide of myelin proteolipid protein (PLP), peptide 139-151, which induces experimental allergic encephalomyelitis in SJL/J (H-2s) mice. We have now identified an additional determinant, PLP residues 178-191, that is also a potent encephalitogen in this strain. When PLP peptide 178-191 was compared with peptide 139-151 on an equimolar basis, the day of onset of disease induced by PLP 178-191 was earlier, but the incidence, severity, and histologic features were indistinguishable. Lymph node cells from animals immunized with the whole PLP molecule responded to both PLP 178-191 and 139-151, suggesting immunologic codominance of the two epitopes. PLP 178-191 elicited stronger proliferative responses and this may relate to the earlier onset of disease induced with this peptide. Two CD4+, peptide-specific, I-A(s)-restricted T cell lines, selected by stimulation of lymph node cells with either PLP 178-191 or 139-151, were each encephalitogenic in naive syngeneic mice. The presence of multiple encephalitogenic codominant PLP epitopes within a single mouse strain emphasizes the complexity of the immune response to PLP and its potential as a target Ag in autoimmune demyelinating diseases.
Greer
J M
JM
Department of Biochemistry, E. K. Shriver Center, Waltham, MA 02254.
Kuchroo
V K
VK
Sobel
R A
RA
Lees
M B
MB
D000595:Amino Acid Sequence; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000737:chemistry / Q000276:immunology*; D018991:Myelin Proteolipid Protein; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010455:Peptides