Multiple, spatially distinct T cell epitopes within a pathogenic 123 residue cyanogen bromide peptide of bovine retinal s-antigen.
We have examined the T cell specificity of a Lewis rat T cell line (R208) specific for a pathogenic, 123 residue cyanogen bromide produced peptide of bovine S-antigen by using two independent sets of overlapping synthetic peptides representing the entire length of the 123 residue fragment. S-antigen, a 48 kDa immunopathogenic photoreceptor cell autoantigen induces T cell mediated experimental autoimmune uveoretinitis (EAU) in experimental animals. Extensive analyses revealed a heterogenous response by the R208 line to the panel of synthetic peptides, proliferating weakly to 4 distinct sites. Unexpectedly, peptides representing sequences (residues 286-297 and 303-320 of bovine S-antigen) known to actively induce the autoimmune pathology were unable to significantly stimulate the R208 line as assessed by proliferation assays. Similarly, attempts to isolate T cells specific for these sequences from the R208 line have proven unsuccessful. However, two sequences, residues 253-269 and 273-289, sufficiently stimulated R208 cells to allow isolation of sub-lines, R208:26 and R208:28, respectively. Neither of these peptides actively induce an autoimmune response. R208:26 does not transfer EAU and R208:28 transfers moderate EAU. As a control, we are able to isolate a pathogenic T cell line (R502) specific for the actively pathogenic sequence, residues 303-320, when this peptide is used as the immunogen. However, the R502 line proliferates to peptides (e.g. 305-322) which do not contain residues 303 and 304 which are critical for the active induction of disease. These results show a multiplicity of distinct T cell epitopes within a relatively small region of S-antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
Fling
S P
SP
Department of Microbiology, University of Minnesota, Minneapolis.
Gregerson
D S
DS
Obritsch
W F
WF
Boyce-Jacino
M
M
Merryman
C F
CF
Donoso
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D019393:Arrestin; D002417:Cattle; D002460:Cell Line; D003488:Cyanogen Bromide; D000939:Epitopes / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D005136:Eye Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D015723:Gene Library; D007116:Immunization, Passive; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D019393:Arrestin; D000939:Epitopes; D005136:Eye Proteins; D010446:Peptide Fragments; D003488:Cyanogen Bromide