title: Influence of protein-quaternary structure on antigen processing.
abstract: T cell recognition of the quaternary structure of human chorionic gonadotropin (hCG), resulting from the association between its alpha (hCG-alpha) and beta (hCG-beta) subunits, was analyzed using hCG-alpha and hCG-beta T cell hybridomas produced in BALB/c mice. First, the fine specificity of these T cell hybridomas was determined, enabling us to divide hCG-alpha-specific T cell hybridomas into two groups. Group I recognized the hCG-alpha(61-81) region, and group II responded to the hCG-alpha(50-70) part of the molecule. Two groups of hCG-beta-specific T cell hybridomas, designated groups III and IV, were analyzed and found to respond to the C- and the N-terminal parts of the hCG-beta(1-22) peptide, respectively. Moreover, we observed that the nature of APC influenced Ag recognition by hCG-beta T cell hybridomas from group IV, but not by other selected T cell hybridomas. We then showed that recognition of the hCG alpha/beta dimer by alpha-specific T cell hybridomas was dramatically reduced compared to both free hCG-alpha and heat-dissociated hCG alpha/beta molecules. In contrast, hCG-beta hybridomas exhibited comparable responses to the free beta subunit and the hCG dimer. Experiments using a dimeric molecule assembled from the alpha-subunit of human follicle-stimulating hormone, which is identical to hCG-alpha, and the beta-subunit of human follicle-stimulating hormone, which is homologous to hCG-beta, confirmed that the three-dimensional structure of the complex rather than the primary structure of the beta-subunit plays a critical role in the processing pathway. Finally, kinetic experiments showed that the presentation of hCG-alpha T cell epitopes differed depending upon whether the alpha-subunit was in its free or combined form. In contrast, the kinetic expression of hCG-beta T cell epitopes appeared to be independent of the quaternary structure of hCG. Thus, conformational alterations resulting from the alpha/beta subunit association mainly influenced processing of the alpha-subunit in its complexed form, rather than processing of the combined beta-subunit. The effect of protein-quaternary structure on T cell recognition may represent a new element in our understanding of the processing and presentation of oligomeric molecules.
authors.affiliation: Laboratoire d'Immunologie des Tumeurs CNRS URA 1484, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Rouas
authors.forename: S
authors.initials: S
authors.lastname: Christophe
authors.forename: F
authors.initials: F
authors.lastname: Housseau
authors.forename: D
authors.initials: D
authors.lastname: Bellet
authors.forename: J G
authors.initials: JG
authors.lastname: Guillet
authors.forename: J M
authors.initials: JM
authors.lastname: Bidart
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D002478:Cells, Cultured; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry* / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015292:Glycoprotein Hormones, alpha Subunit