title: HLA class II defects in Burkitt lymphoma: bryostatin-1-induced 17 kDa protein restores CD4+ T-cell recognition.
abstract: While the defects in HLA class I-mediated Ag presentation by Burkitt lymphoma (BL) have been well documented, CD4+ T-cells are also poorly stimulated by HLA class II Ag presentation, and the reasons underlying this defect(s) have not yet been fully resolved. Here, we show that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. The observed defect was not associated with low levels of BL-expressed costimulatory molecules, as addition of external co-stimulation failed to result in BL-mediated CD4+ T-cell activation. We further demonstrate that BL cells express the components of the class II pathway, and the defect was not caused by faulty Ag/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Treatment of BL with broystatin-1, a potent modulator of protein kinase C, led to significant improvement of functional class II Ag presentation in BL. The restoration of immune recognition appeared to be linked with an increased expression of a 17 kDa peptidylprolyl-like protein. These results demonstrate the presence of a specific defect in HLA class II-mediated Ag presentation in BL and reveal that treatment with bryostatin-1 could lead to enhanced immunogenicity.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Azim
authors.initials: A
authors.lastname: Hossain
authors.forename: Jason M
authors.initials: JM
authors.lastname: God
authors.forename: Faisal F Y
authors.initials: FF
authors.lastname: Radwan
authors.forename: Shereen
authors.initials: S
authors.lastname: Amria
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Bethard
authors.forename: Azizul
authors.initials: A
authors.lastname: Haque
mesh_terms: D017951:Antigen Presentation; D000970:Antineoplastic Agents / Q000494:pharmacology*; D054713:Bryostatins / Q000494:pharmacology*; D002051:Burkitt Lymphoma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D054713:Bryostatins; D006681:HLA-D Antigens; D007376:Interleukin-2; C046785:bryostatin 1