A single amino acid mutation in a protein antigen abrogates presentation of certain T cell determinants.
Nase-specific T cell recognize the 86-100 peptide in association with B10.A APC. Clone N40 recognizes the 86-100 peptide in association with B10.A (Ek alpha Ek beta) and B10.A (5R) (Ek alpha Eb beta) APCs. We demonstrate here that a single amino acid substitution in the staphylococcal nuclease protein alters the structure of the processed peptide such that the T cell epitope recognized by clone N40 was only available for recognition in conjunction with B10.A (5R) but not the B10.A APCs. Other Nase-specific T cells recognize the mutant nuclease, and a synthetic peptide corresponding to the immunodominant region of the mutant protein was stimulatory for all the Nase-specific T cells. These results suggest that the mutation either affects the processing of the protein into antigenic peptides or affects the conformation of the processed fragment differently from that of the peptide.
Finnegan
A
A
Department of Internal Medicine, Rush-Presbyterian-St. Luke's Medical School, Chicago, Illinois 60612.
Amburgey
C F
CF
D000818:Animals; D000939:Epitopes; D008297:Male; D051379:Mice; D008836:Micrococcal Nuclease / Q000276:immunology*; D009154:Mutation; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D008836:Micrococcal Nuclease