title: Peptide binding to mixed isotype Abeta(d)Ealpha(d) class II histocompatibility molecules.
abstract: Previous studies have demonstrated that mixed isotype A beta(d) E alpha(d) molecules are expressed in transfected cell lines and that the level of expression is very low in normal B cells from H-2(d) mice. T-cell responses restricted by A beta(d) E alpha(d) are induced in H-2(d) mice immunized with the synthetic peptides YL2 and FL2 or with sperm whale myoglobin, despite the low concentration of mixed isotype molecules expressed on antigen-presenting cells. In the present study, the peptide binding behavior of A beta(d) E alpha(d) was investigated. A peptide from the cytoplasmic domain of invariant chain, I(1-18), was observed to bind with high affinity to purified A beta(d) E alpha(d). Binding was optimal at pH 5, indicating that these molecules prefer to bind peptide in the acidic environment of endosomal compartments similar to other murine class II proteins. YL2 and FL2 bind to A beta(d) E alpha(d) with slightly lower affinity. The selective restriction of YL2- and FL2-specific T cells to mixed isotype molecules was accounted for by the observation that these peptides do not bind to either I-E(d) or I-A(d). By contrast, myoglobin peptides bind to both parental and mixed isotype molecules. None of the A beta(d) E alpha(d)-restricted peptide determinants bind to A beta(d) E alpha(d) with extremely high affinity. Thus it is unlikely that these peptides occupy an unusually high fraction of mixed isotype molecules during antigen presentation in vivo. It is more likely that the presence of a subpopulation of high-affinity T cells capable of being stimulated by very low concentrations of A beta(d) E alpha(d)/peptide complexes is responsible for the unusual A beta(d) E alpha(d)-restricted response observed with some antigens.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Moore
authors.forename: M
authors.initials: M
authors.lastname: Zauderer
authors.forename: K
authors.initials: K
authors.lastname: Natarajana
authors.forename: P E
authors.initials: PE
authors.lastname: Jensen
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006183:H-2 Antigens / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007519:Isoantigens / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009211:Myoglobin / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D009211:Myoglobin; D010455:Peptides