Multiple defects in HLA class II-mediated immune recognition of Burkitt's lymphoma (P5055)

Abstract

Abstract While Burkitt Lymphoma (BL) has a well-known defect in HLA class I-mediated Ag 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 costimulatory molecules on BL cells, as addition of external costimulation failed to elicit CD4+ T cell activation by BL. Further, the defect was not caused by faulty Ag/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 which impaired class II-mediated Ag presentation and CD4+ T cell recognition. Biochemical analysis showed that these molecules were greater than 30 kDa in size, and proteinaceous in nature. In addition, BL was found to have decreased expression of a 47 kDa enolase-like molecule which enhances class II-mediated Ag presentation in B cells, macrophage and dendritic cells, but not in BL. These findings demonstrate that BL likely has multiple defects in HLA class II-mediated Ag presentation and immune recognition, which may be exploited for future immunotherapies.