Chemokine receptor targeting efficiently directs antigens to MHC class I pathways and elicits antigen-specific CD8+ T-cell responses

Chemokines are key controllers of cell trafficking and are involved in numerous pathologic and inflammatory conditions. However, the fate of a chemokine ligand, once it is endocytosed with its receptor, remains obscure. Here, using chemokine–tumor antigen fusion constructs, we demonstrate for the first time that chemokines are internalized to early/late endosomal and lysosomal compartments through a clathrin-dependent process and subsequently delivered to the cytosol for proteasomal processing, facilitating efficient cross-presentation to the TAP-1–dependent MHC class I processing pathway. These data not only elucidate the intracellular fate of chemokine ligands upon receptor uptake, but also demonstrate the superior carrier potency of chemokines for delivering self-antigens to both class I and II processing pathways to induce CD8+ and CD4+ T-cell responses

Integration of clinical anatomical sciences in medical education: Design, development and implementation strategies

For the last 20 years, undergraduate medical education has seen a major curricular reform movement toward integration of basic and clinical sciences. The rationale for integrated medical school curricula focuses on the application of knowledge in a clinical context and the early ability to practice key skills such as critical thinking and clinical problem-solving. The method and extent of discipline integration can vary widely from single sessions to entire programs. A challenge for integrated curricula is the design of appropriate assessments. The goal of this review is to provide a framework for clinical anatomy educators with definitions of integration, examples of existing integration models, strategies, and instructional methods that promote integration of basic and clinical sciences