Conformation-dependent recognition of a protein by T cells requires presentation without processing.
Presentation of a protein antigen to T cells is believed to follow its intracellular breakdown by the antigen-presenting cell, with the fragments constituting the trigger of immune recognition. It should then be expected that T-cell recognition of protein antigens in vitro will be independent of protein conformation. Three T-cell lines were made by passage in vitro with native lysozyme of T cells from two mouse strains (B10.BR and DBA/1) that had been primed with the same protein. These cell lines responded well to native lysozyme and very poorly to unfolded (S-sulphopropyl) lysozyme. The response of the T-cell lines to the antigen was major histocompatibility complex (MHC)-restricted. A line from B10.BR was selected for further studies. This line responded to the three surface-simulation synthetic sites of lysozyme (representing the discontinuous antigenic, i.e. antibody binding, sites) and analogues that were extended to a uniform size by a nonsense sequence. T-cell clones prepared from this line were specific to native lysozyme and did not respond to the unfolded derivative. Furthermore, several of these clones showed specificity to a given surface-simulation synthetic site. The exquisite dependency of the recognition by the clones on the conformation of the protein antigen and their ability to recognize the surface-simulation synthetic sites indicate that the native (unprocessed) protein was the trigger of MHC-restricted T-cell recognition.
Atassi
M Z
MZ
Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
Bixler
G S
GS
Yokoi
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology*; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D009113:Muramidase