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1.  Distinct Pathways Generate Peptides from Defective Ribosomal Products for CD8+ T Cell Immunosurveillance 
To understand better the endogenous sources of MHC class I peptide ligands, we generated an antigenic reporter protein whose degradation is rapidly and reversibly controlled with Shield-1, a cell-permeant drug. Using this system, we demonstrate that defective ribosomal products (DRiPs) represent a major and highly efficient source of peptides and are completely resistant to our attempts to stabilize the protein. Although peptides also derive from nascent Shield-1–sensitive proteins and “retirees” created by Shield-1 withdrawal, these are much less efficient sources on a molar basis. We use this system to identify two drugs—each known to inhibit polyubiquitin chain disassembly—that selectively inhibit presentation of Shield-1–resistant DRiPs. These findings provide the initial evidence for distinct biochemical pathways for presentation of DRiPs versus retirees and implicate polyubiquitin chain disassembly or the actions of deubiquitylating enzymes as playing an important role in DRiP presentation.
doi:10.4049/jimmunol.1003096
PMCID: PMC3408966  PMID: 21228349
2.  Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells 
The Journal of Experimental Medicine  2011;208(12):2511-2524.
CCR5-binding chemokines produced in the draining lymph node after vaccinia virus infection guide naive CD8+ T cells toward DCs and away from the macrophage-rich zone, thereby facilitating optimal CD8+ T cell activation and cytokine production.
Naive antiviral CD8+ T cells are activated in the draining LN (DLN) by dendritic cells (DCs) presenting viral antigens. However, many viruses infect LN macrophages, which participate in initiation of innate immunity and B cell activation. To better understand how and why T cells select infected DCs rather than macrophages, we performed intravital microscopy and ex vivo analyses after infecting mice with vaccinia virus (VV), a large DNA virus that infects both LN macrophages and DCs. Although CD8+ T cells interact with both infected macrophages and DCs in the LN peripheral interfollicular region (PIR), DCs generate more frequent and stable interactions with T cells. VV infection induces rapid release of CCR5-binding chemokines in the LN, and administration of chemokine-neutralizing antibodies diminishes T cell activation by increasing T cell localization to macrophages in the macrophage-rich region (MRR) at the expense of PIR DCs. Similarly, DC ablation increases both T cell localization to the MRR and the duration of T cell–macrophage contacts, resulting in suboptimal T cell activation. Thus, virus-induced chemokines in DLNs enable antiviral CD8+ T cells to distinguish DCs from macrophages to optimize T cell priming.
doi:10.1084/jem.20102545
PMCID: PMC3256957  PMID: 22042976

Results 1-2 (2)