Physiological-range temperature changes modulate cognate antigen processing and presentation mediated by lipid raft-restricted ubiquitinated B cell receptor molecules.
Physiological-range temperature changes modulate cognate antigen processing and presentation mediated by lipid raft-restricted ubiquitinated B cell receptor molecules.
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DOI:
10.4049/jimmunol.1001653
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发表时间:
2010-11-01
期刊:
影响因子:
--
通讯作者:
Drake JR
中科院分区:
文献类型:
--
作者:
Katkere B;Rosa S;Caballero A;Repasky EA;Drake JR
B cell receptor (BCR)-mediated antigen processing and presentation is critical to the initiation and control of a humoral immune response. Trafficking of internalized antigen-BCR (Ag-BCR) complexes to intracellular antigen processing compartments is driven by ubiquitination of the cytoplasmic domain of the BCR. Using a biochemical approach, it is here established that ubiquitinated Ag-BCR complexes are formed via a signaling-dependent mechanism and restricted to plasma membrane lipid rafts. Since the structure of lipid rafts is temperature sensitive, the impact of physiological range temperature changes (33–39°C) on lipid raft-dependent and independent BCR functions was investigated. While the kinetics of lipid raft independent BCR internalization are unaffected by temperature changes within this range, raft-dependent BCR signaling and ubiquitination as well as BCR-mediated antigen processing are significantly impacted. When compared to 33°C (peripheral body temperature), the extent and duration of Ag-BCR ubiquitination is increased and prolonged at 37–39°C (normal to febrile temperature). As might be expected, increased temperature also accelerates the overall kinetics of Ag-BCR degradation. Interestingly, at 33°C the expression of peptide-class II complexes derived from the BCR-mediated processing of cognate antigen is profoundly slowed, whereas the kinetics of expression of peptide-class II complexes derived from fluid-phase antigen processing remain unchanged. These results establish the effect of physiological range temperature changes on multiple lipid raft-dependent BCR functions including the processing and presentation of cognate antigen, suggesting one mechanism by which physiological range temperature changes such as fever may impact the initiation and /or maturation of a humoral immune response.
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