title: Local structure of a peptide contact site on Ak alpha.
abstract: We have sought to determine how much amino acid diversity is tolerable at position 69 of the Ak alpha chain, a position previously implicated as a peptide contact site. Slot-machine mutagenesis was used to create a set of 11 mutant Ak alpha cDNAs, each specifying a different amino acid at position 69. These cDNAs were individually expressed in L cells together with a wild-type Ak beta cDNA to produce a panel of mutant antigen-presenting cell lines. The ability of each member of this panel to present a hen egg lysozyme and a bovine ribonuclease peptide to various T hybridomas was assessed. We found that a surprising degree of amino acid diversity is tolerable at Ak alpha position 69: even charged (Glu, Arg) or bulky (Trp, Tyr) residues can be accommodated without abrogating cell-surface expression of Ak, peptide binding to it, or T cell recognition of it. We discuss the implications of these findings for models of T cell recognition of the class II molecule/antigen duplex.
authors.affiliation: Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS et Unité 184 de l'Inserm, Faculté de Médecine, Strasbourg, France.
authors.forename: B Y
authors.initials: BY
authors.lastname: Wei
authors.forename: N
authors.initials: N
authors.lastname: Gervois
authors.forename: G
authors.initials: G
authors.lastname: Mer
authors.forename: L
authors.initials: L
authors.lastname: Adorini
authors.forename: C
authors.initials: C
authors.lastname: Benoist
authors.forename: D
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000235:genetics; D006825:Hybridomas / Q000276:immunology; D007739:L Cells / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell