Mechanisms of major histocompatibility complex class II-restricted processing and presentation of the V antigen of Yersinia pestis
Article first published online: 18 AUG 2006
Volume 119, Issue 3, pages 385–392, November 2006
How to Cite
Shim, H.-K., Musson, J. A., Harper, H. M., McNeill, H. V., Walker, N., Flick-Smith, H., Von Delwig, A., Williamson, E. D. and Robinson, J. H. (2006), Mechanisms of major histocompatibility complex class II-restricted processing and presentation of the V antigen of Yersinia pestis. Immunology, 119: 385–392. doi: 10.1111/j.1365-2567.2006.02447.x
- Issue published online: 18 AUG 2006
- Article first published online: 18 AUG 2006
- Received 27 February 2006; revised 30 June 2006; accepted 30 June 2006.
- antigen presentation;
- MHC class II;
- T cells;
- vaccine antigen
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.