Processing requirements of two acetylcholine receptor derived peptides for binding to antigen presenting cells and stimulation of murine T cell lines.
We have previously identified two myasthenogenic T cell epitopes of the human acetylcholine receptor (AChR) alpha subunit, peptides p195-212 and p259-271. These peptides were the immunodominant T cell epitopes of AChR in SJL and BALB/c mice respectively, and only cryptic in C3H.SW strain. In order to find out whether these mouse strains differ in their requirements for processing of the same T cell epitopes, we used p195-212 specific T cell lines from SJL, TCSJL195-212, and C3H.SW, TCSW195-212, mice, and p259-271 specific T cell lines from BALB/c, TCBALB/c259-271, and C3H.SW, TCSW259-271, mice. The peptide-specific proliferative responses of the lines TCSW195-212 and TCSW259-271, originated from strains in which these peptides are cryptic epitopes, were inhibited significantly in the presence of several inhibitors of proteases or glutaraldehyde-fixed antigen presenting cells (APC). In contrast, the proliferative responses of the lines TCSJL195-212 and TCBALB/c259-271, established from strains in which these peptides are immunodominant, were only slightly affected by the above inhibitors or by fixation of the APC. Using a direct binding assay of biotinylated peptides to live intact APC, we showed that peptides p195-212 and p259-271 preserved their binding capacity to APC of SJL and BALB/c mice respectively when processing was inhibited. Thus, the AChR peptides that represent cryptic T cell epitopes have to be processed before they can be recognized by T cells, whereas no further processing is necessary for APC presentation and T cell stimulation when these peptides are immunodominant epitopes.
Zisman
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Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Mozes
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D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D010446:Peptide Fragments; D011480:Protease Inhibitors; D011950:Receptors, Cholinergic