title: Antigen three-dimensional structure guides the processing and presentation of helper T-cell epitopes.
abstract: Antigen three-dimensional structure potentially controls presentation of CD4(+) T-cell epitopes by limiting the access of proteolytic enzymes and MHC class II antigen-presenting proteins. The protease-sensitive mobile loops of Hsp10s from mycobacteria, Escherichia coli, and bacteriophage T4 (T4Hsp10) are associated with adjacent immunodominant helper T-cell epitopes, and a mobile-loop deletion in T4Hsp10 eliminated the protease sensitivity and the associated epitope immunodominance. In the present work, protease-sensitivity and epitope presentation was analyzed in a group of T4Hsp10 variants. Two mobile-loop sequence variants of T4Hsp10 were constructed by replacing different segments of the mobile loop with an irrelevant sequence from hen egg lysozyme. The variant proteins retained native-like structure, and the mobile loops retained protease sensitivity. Mobile-loop deletion and reconstruction affected the presentation of two epitopes according to whether the epitope was protease-independent or protease-dependent. The protease-independent epitope lies within the mobile loop, and the protease-dependent epitope lies in a well-ordered segment on the carboxy-terminal flank of the mobile loop. The results are consistent with a model for processing of the protease-dependent epitope in which an endoproteolytic nick in the mobile-loop unlocks T4Hsp10 three-dimensional structure, and then the epitope becomes available for binding to the MHC protein.
authors.affiliation: Department of Biochemistry, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Carmicle
authors.forename: N Kalaya
authors.initials: NK
authors.lastname: Steede
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Landry
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018835:Chaperonin 10 / Q000737:chemistry / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D018835:Chaperonin 10; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes