Presentation of insulin and insulin A chain peptides to mouse T cells: involvement of cysteine residues.
The requirements for insulin presentation and recognition by A alpha b A beta b- and A alpha b A beta k-restricted mouse T cells were studied using a variety of derivatives of the insulin A chain. It was found that A chain peptides with irreversibly blocked Cys residues are non-stimulatory for the T cells. This suggests that at least one of the Cys residues is essential for recognition. On the other hand, all A chain peptides containing Cys residues modified in a way reversible by reaction with thiols are stimulatory yet differ in antigenic potency. All these A chain derivatives including a 14 amino acid fragment require uptake by antigen presenting cells (APC) for efficient presentation. Differences in stimulatory potency between the A chain peptides derived from the same insulin appear to be mainly due to the efficiency of uptake and/or processing by APC. Based on these findings we propose that processing in the case of insulin and its A chain derivatives involves the reductive deblocking of Cys residues or the rearrangement of disulfide bonds apart from a possible proteolytic cleavage. The same may apply to other proteins if Cys residues in the presented peptides are important for the interaction with Ia or the T cell receptor.
Hampl
J
J
Institut für Immunologie der Joh. Gutenberg Universität, Mainz, Germany.
Gradehandt
G
G
Plachov
D
D
Gattner
H G
HG
Kalbacher
H
H
Voelter
W
W
Meyer-Delius
M
M
Rüde
E
E
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002417:Cattle; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D066298:In Vitro Techniques; D007328:Insulin / Q000737:chemistry / Q000276:immunology*; D007377:Interleukin-3 / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D007377:Interleukin-3; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D002738:Chloroquine; D003545:Cysteine