Identification of an N-terminally acetylated encephalitogenic epitope in myelin proteolipid apoprotein for the Lewis rat.
Proteolipid apoprotein (PLP) is a major component of the central nervous system myelin. As such, it is capable of inducing experimental allergic encephalomyelitis (EAE) in many subhuman species. On the basis of a putative MHC class II binding motif in Lewis rats (RT-1B1) recently identified in our laboratory, the present study identifies one pathogenic T cell epitope of PLP for the Lewis rat, located in the area between amino acid residues 217 and 240. Four overlapping synthetic peptides derived from this region were tested for their antigenicity and encephalitogenicity. Although the longer peptides could not induce EAE in the Lewis rats in their "theoretically" native form after immunization, they were endowed with encephalitogenic ability when modified by N-terminal acetylation. All animals immunized with N-acetylated peptides PLP 217-233 and PLP 224-240 developed inflammation in the lower spinal cord, but with very low incidence of clinical EAE (1 of 12). In contrast, none of the animals immunized with nonacetylated peptides developed either clinical or histologic EAE. Mild inflammation of the spinal cord was also found in two of four rats immunized with N-acetylated peptide PLP 220-234. The animals immunized with the decapeptide, N-acetylated PLP 224-233, did not develop inflammation of the spinal cord. Despite the low incidence of clinical disease, it was possible to generate vigorous T cell lines against all the peptides synthesized from this region of PLP.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhao
W
W
Department of Pathology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756.
Wegmann
K W
KW
Trotter
J L
JL
Ueno
K
K
Hickey
W F
WF
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001059:Apoproteins / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000032:analysis*; D005260:Female; D007114:Immunization; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000276:immunology*; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology
D001059:Apoproteins; D000939:Epitopes; D007376:Interleukin-2; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments