title: Disruption of HLA class II antigen presentation in Burkitt lymphoma: implication of a 47,000 MW acid labile protein in CD4+ T-cell recognition.
abstract: While Burkitt lymphoma (BL) has a well-known defect in HLA class I-mediated antigen presentation, the exact role of BL-associated HLA class II in generating a poor CD4(+) T-cell response remains unresolved. Here, we found that BL cells are deficient in their ability to optimally stimulate CD4(+) T cells via the HLA class II pathway. This defect in CD4(+) T-cell recognition was not associated with low levels of co-stimulatory molecules on BL cells, as addition of external co-stimulation failed to elicit CD4(+) T-cell activation by BL. Further, the defect was not caused by faulty antigen/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Interestingly, functional class II-peptide complexes were formed at acidic pH 5·5, which restored immune recognition. Acidic buffer (pH 5·5) eluate from BL cells contained molecules that impaired class II-mediated antigen presentation and CD4(+) T-cell recognition. Biochemical analysis showed that these molecules were greater than 30,000 molecular weight in size, and proteinaceous in nature. In addition, BL was found to have decreased expression of a 47,000 molecular weight enolase-like molecule that enhances class II-mediated antigen presentation in B cells, macrophages and dendritic cells, but not in BL cells. These findings demonstrate that BL likely has multiple defects in HLA class II-mediated antigen presentation and immune recognition, which may be exploited for future immunotherapies.
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, and Children's Research Institute, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: God
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Christine A
authors.initials: CA
authors.lastname: Cameron
authors.forename: Shereen
authors.initials: S
authors.lastname: Amria
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Bethard
authors.forename: Azizul
authors.initials: A
authors.lastname: Haque
mesh_terms: D002051:Burkitt Lymphoma / Q000276:immunology* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008970:Molecular Weight; D010751:Phosphopyruvate Hydratase / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D010751:Phosphopyruvate Hydratase
keywords: Burkitt lymphoma; HLA class II; antigen presentation; enolase-like molecules; immune escape