Induction of experimental allergic encephalomyelitis by myelin proteolipid-protein-specific T cell clones and synthetic peptides.
Proteolipid protein (PLP) is the major protein of central nervous system (CNS) myelin. SJL(H-2s) mice immunized with a synthetic peptide corresponding to PLP residues 139-151 (HSLGKWLGHPDKF) develop acute experimental allergic encephalomyelitis (EAE). In the present study a T cell line and 4 clones were derived from SJL/J mice following immunization with this synthetic peptide. Severe clinical and histological EAE could be induced by adoptive transfer of the peptide-specific T cell line and 3 of 4 T cell clones. The T cell line/clones all responded strongly to PLP peptide 139-151 in in vitro proliferative assays. However, two different reactivity patterns emerged when truncated PLP peptides 141-150 and 141-149 were tested, suggesting that more than 1 epitope may be present within the PLP 139-151 determinant. To evaluate the encephalitogenic potential of the truncated peptides, we compared the ability of 2 truncated PLP peptides to induce EAE in vivo and proliferative responses in vitro. Immunization with PLP peptide 141-150 induced acute EAE in about 70% of mice tested, but PLP peptide 141-149 induced a comparatively mild form of EAE in 4 out of 9 mice tested. Lymph node cells from mice immunized with these peptides showed in vitro proliferative responses to each of the peptides, but the response to peptide 139-151 was always strongest. These combined in vivo and in vitro data further define the epitopes involved in PLP-induced EAE in SJL mice. Furthermore, the availability of multiple PLP-specific T cell clones will enable us to study the diversity of the T cell repertoire to PLP.
Kuchroo
V K
VK
Department of Pathology, Harvard Medical School, Boston, Mass.
Sobel
R A
RA
Yamamura
T
T
Greenfield
E
E
Dorf
M E
ME
Lees
M B
MB
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000209:etiology / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D007114:Immunization; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D018991:Myelin Proteolipid Protein; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D000939:Epitopes; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010455:Peptides