title: T cell hybridomas to study MHC-II restricted B-cell receptor-mediated antigen presentation by human B cells.
abstract: MHC-II antigen presentation by B cells is essential in order for B cells to receive optimal costimulation from helper CD4+ T cells. This process is facilitated and focused through the extremely efficient uptake, processing, and presentation of antigen recognized by an individual B cell's unique B-cell receptor (BCR). The investigation of human B-cell antigen presentation has been limited by the varied specificity of BCR found in the mixed populations of B cells in vivo. As a result, there is no readily available method to measure BCR-mediated antigen presentation in this heterogeneous population of B cells. We have overcome this limitation by developing HLA-DR-restricted T-cell lines capable of recognizing a specific antigen taken up via the BCR and presented by the mixed B-cell population through this physiologically relevant mechanism. BCR-mediated presentation was enhanced >4 logs compared to presentation by B cells taking up the antigen through nonspecific mechanisms. The studies presented here characterize T-cell hybridoma lines developed for HLA-DRB1*0101+ and HLA-DRB1*1501+ B cells, but clones could be generated for other HLA-DR types using the methods described. These hybridomas have potential applications including study of the mechanisms of BCR-mediated enhancement of presentation, determination of adjuvant effects on presentation, and optimization of vaccine antigen preparations. Therefore, these T-cell lines could significantly facilitate the study of BCR-mediated antigen presentation required by T helper cell-dependent vaccines in humans.
authors.affiliation: Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, VA, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Bartley
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002469:Cell Separation / Q000379:methods*; D003429:Cross Reactions; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology*; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell