Mechanisms of major histocompatibility complex class II-restricted processing and presentation of the V antigen of Yersinia pestis

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Abstract
We mapped mouse CD4 T‐cell epitopes located in three structurally distinct regions of the V antigen of Yersinia pestis. T‐cell hybridomas specific for epitopes from each region were generated to study the mechanisms of processing and presentation of V antigen by bone‐marrow‐derived macrophages. All three epitopes required uptake and/or processing from V antigen as well as presentation to T cells by newly synthesized major histocompatibility complex (MHC) class II molecules over a time period of 3–4 hr. Sensitivity to inhibitors showed a dependence on low pH and cysteine, serine and metalloproteinase, but not aspartic proteinase, activity. The data indicate that immunodominant epitopes from all three structural regions of V antigen were presented preferentially by the classical MHC class II‐restricted presentation pathway. The requirement for processing by the co‐ordinated activity of several enzyme families is consistent with the buried location of the epitopes in each region of V antigen. Understanding the structure–function relationship of multiple immunodominant epitopes of candidate subunit vaccines is necessary to inform choice of adjuvants for vaccine delivery. In the case of V antigen, adjuvants designed to target it to lysosomes are likely to induce optimal responses to multiple protective T‐cell epitopes.