z-logo
Premium
Disruption of HLA class II antigen presentation in Burkitt lymphoma: implication of a 47 000 MW acid labile protein in CD4 + T‐cell recognition
Author(s) -
God Jason M.,
Zhao Dan,
Cameron Christine A.,
Amria Shereen,
Bethard Jennifer R.,
Haque Azizul
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12281
Subject(s) - antigen , antigen presentation , human leukocyte antigen , mhc class ii , immune system , t cell , biology , antigen processing , antigen presenting cell , microbiology and biotechnology , mhc class i , immunology , major histocompatibility complex , chemistry
Summary 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.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here