Sequence 104-117 of myelin proteolipid protein is a cryptic encephalitogenic T cell determinant for SJL/J mice.
Immunization of animals with myelin proteolipid protein (PLP) causes experimental autoimmune encephalomyelitis (EAE), a disease model that shares many features with human multiple sclerosis (MS). The SJL/J (H-2s) mouse is widely used in EAE studies because of its high disease susceptibility. Previous studies have shown that sequences 139-151 HCLGKWLGHPDKF and 178-191 NTWTTCQSIAFPSK represent distinct co-immunodominant encephalitogenic determinants of PLP for SJL/J mice. In the present study, we identify a third distinct PLP encephalitogenic peptide for SJL/J mice. Following immunization with PLP 104-117 KTTICGKGLSATVT, 10/14 SJL/J mice developed clinical and histological EAE with a mean time of onset of 38 days (18-65 days). T cell lines generated from SJL/J mice immunized with p104-117 were predominantly (> 90%) CD3+, CD4+, alpha beta TCR+, CD8dim, gamma delta TCRdim T cells and responded in an Ag-specific, I-A(s)-restricted manner to p104-117. Upon adoptive transfer of 16-40 x 10(6) T line cells, EAE was produced in naive SJL/J recipients 20-34 days after transfer. The delayed onset of both active and passive disease may be related to the non-immunodominant, cryptic nature of p104-117 in SJL/J mice. Lymph node cells from SJL/J mice immunized with either whole PLP or with pooled encephalitogenic PLP peptides responded to challenge with the immunodominant PLP determinants p139-151 and p178-191 but did not respond to p104-117. The existence of three distinct PLP encephalitogenic T cell determinants for SJL/J mice suggests that susceptibility to EAE and perhaps MS may be related to promiscuous T cell recognition of multiple myelin protein determinants.
Tuohy
V K
VK
Department of Immunology, Cleveland Clinic Foundation, OH 44195.
Thomas
D M
DM
D000595:Amino Acid Sequence; D000818:Animals; D001059:Apoproteins / Q000276:immunology*; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology; D000939:Epitopes; D005260:Female; D007114:Immunization; D016219:Immunotherapy, Adoptive; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000276:immunology*; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001059:Apoproteins; D000939:Epitopes; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments