Modulation of restricted class II T cell responses by peptides derived from self class II molecule.
We have explored the possibility of using peptides derived from a major histocompatibility complex (MHC) class II (I-Ab) molecule to modulate I-Ab-restricted T cell responses. Six peptides spanning the polymorphic regions of I-Ab were analyzed for competitive binding to the I-Ab molecule, and for efficacies in blocking I-Ab-specific T cell response. Only PB1 (residues 75-91 of beta chain) bound the I-Ab molecule with high affinity. When these MHC-derived peptides were administered simultaneously with antigen, PB1 effectively inhibited I-Ab-restricted T cell responses as well as another peptide PB2 (residues 59-78 of beta chain). PB2 inhibited specific T cell response only when it was administered simultaneously with antigen. Since PB2 is a weak binder of I-Ab, an additional mechanism must account for its inhibitory activity. Both PB1 and PB2 peptides elicited specific T cell responses, indicating that these peptides were not tolerogenic in syngeneic mice. However, the induction of T cells in response to PB1 and PB2 did not increase reactivity to I-Ab. MHC class II-derived peptides thus can be used to regulate T cell responses without the risk of autoreactivity.
Li
W F
WF
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, R.O.C.
Fan
M D
MD
Pan
C B
CB
Gefter
M L
ML
Lai
M Z
MZ
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell