Degenerate antigen recognition by CD4+ effector T cells in experimental autoimmune encephalomyelitis.
Peptide-specific tolerance with PLP139-151 peptide analogs was used to compare the fine antigen-specificity requirements at both the inductive and effector phases of relapsing EAE (R-EAE). A PLP139-151 analog peptide containing a single substitution at the primary T cell receptor (TcR) contact residue (A144) did not induce proliferation in PLP139-151-primed CD4+ T cells. In addition, tolerance induced with ECDI-treated. A144-coupled splenocytes failed to prevent the inductive phase of PLP139-151-induced R-EAE or to inhibit the induction of peptide-specific DTH indicating that naive PLP139-151-specific T cells do not react with the A144 peptide analog. In contrast, A144-coupled splenocytes did prevent the expression of the effector phase of R-EAE and inhibited the elicitation of peptide-specific DTH responses upon administration to mice seven days after immunization with PLP139-151. The results provide in vivo evidence that "antigen-experienced' T cells recognize a broader repertoire of antigens than do naive T cells and have important implications for the regulation of immune responses and for advancing our understanding of the pathogenesis and treatment of autoimmune disease.
McRae
B L
BL
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Karandikar
N J
NJ
Miller
S D
SD
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C435023:myelin proteolipid protein (139-151)