title: T cell recognition of flanking residues of murine invariant chain-derived CLIP peptide bound to MHC class II.
abstract: The major site of interaction between MHC class II molecules and invariant chain has been mapped to occupancy of the class II peptide-binding site by the CLIP region of invariant chain. CLIP is also seen as a degradation product of invariant chain and can be found in association with class II as a processing intermediate. Here we analyzed the relative contribution of single amino acids in the murine CLIP (86-102) peptide for binding to I-Ab and I-Ad and for recognition by a CLIP-specific T cell hybridoma. Interestingly, the I-Ab-restricted murine T cell hybridoma that recognizes murine CLIP peptide (86-102) is dependent on Met 102 for activation. This amino acid is outside of the core binding region and in the CLIP/DR3 crystal structure extends outside of the class II peptide-binding site. These data suggest that a T cell epitope presented on CLIP/class II complexes can be located predominantly in flanking residues that extend out of the peptide binding groove of class II.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Naujokas
authors.forename: S
authors.initials: S
authors.lastname: Southwood
authors.forename: S J
authors.initials: SJ
authors.lastname: Mathies
authors.forename: E
authors.initials: E
authors.lastname: Appella
authors.forename: A
authors.initials: A
authors.lastname: Sette
authors.forename: J
authors.initials: J
authors.lastname: Miller
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007930:Leucine / Q000032:analysis; D008715:Methionine / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D008715:Methionine; D007930:Leucine