Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor.
A novel mechanism for inhibition of T cell responses is described. Using the recognition of the influenza hemagglutinin (HA) 307-319 peptide in the context of DR1 class II major histocompatibility complex molecules, we have found that nonstimulatory analogs of the HA peptide preferentially inhibit HA-specific T cells in inhibition of antigen presentation assays. This antigen-specific effect could be generalized to another DR1-restricted peptide, Tetanus toxoid 830-843. Direct binding and cellular experiments indicated that the mechanism responsible was distinct from competition for binding to DR1 molecules. Likewise, negative signaling and induction of T cell tolerance could also be excluded as effector mechanisms. Thus, the most likely mechanism for this effect is engagement of antigen-specific T cell receptors by DR1-peptide analog complexes, which results in antigen-specific competitive blocking of T cell responses by virtue of their capacity to compete with DR1-antigen complexes for binding to the T cell receptor.
De Magistris
M T
MT
Cytel, San Diego, California 92121.
Alexander
J
J
Coggeshall
M
M
Altman
A
A
Gaeta
F C
FC
Grey
H M
HM
Sette
A
A
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D015798:HLA-DR1 Antigen / Q000737:chemistry* / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex; D008954:Models, Biological; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors*; D013745:Tetanus Toxoid / Q000737:chemistry
D000276:Adjuvants, Immunologic; D015798:HLA-DR1 Antigen; D006389:Hemagglutinins, Viral; D011948:Receptors, Antigen, T-Cell; D013745:Tetanus Toxoid