Functional consequences of the binding of MHC class II-derived peptides to MHC class II.
Three MHC class II-derived synthetic peptides (I-A beta (g7)1-16, I-A beta (g7)52-77 and I-A alpha (g7)63-82YC) were analyzed for their ability to bind to syngeneic and allogeneic MHC class II molecules using a whole cell, competitive peptide binding assay. These studies demonstrated that the A beta (g7)1-16 peptide was able to specifically bind to syngeneic as well as to four allogeneic MHC class II molecules. The A alpha (g7)63-82YC peptide bound to self MHC class II molecules with a lower relative affinity and was able to bind to three out of the four allogeneic cells tested. The binding of the three I-A(g7)-derived peptides to the self MHC class II was functionally significant. The A beta (g7)1-16 and A beta (g7)52-77 peptides inhibited the proliferation of a heat shock protein 60 peptide-specific Th1 clone by MHC blockade. Interestingly, the A alpha (g7)63-82YC peptide appeared to interact directly with T cells as pretreatment of the Th1 clone with this peptide resulted in inhibition of antigen-induced proliferation. This phenomenon was analyzed in more detail and it was found that this peptide could behave as a partial agonist. Incubation of T cells with the A alpha (g7)63-82YC peptide resulted in up-regulation of IL-2R alpha chain expression and induction of IFN-gamma secretion. In addition T cells pretreated with this peptide were rendered hyporesponsive to further antigenic stimulation. Thus, a peptide derived from MHC class II may be used in an immunoregulatory capacity.
Feili-Hariri
M
M
Department of Medicine, University of Pittsburgh, PA, USA.
Kao
H
H
Mietzner
T A
TA
Morel
P A
PA
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D018834:Chaperonin 60 / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D018528:ATP-Binding Cassette Transporters; D000276:Adjuvants, Immunologic; D018834:Chaperonin 60; D000949:Histocompatibility Antigens Class II; D010455:Peptides