Current status of alloimmunity

Abstract

Purpose of review The present review aims to highlight the major recent advances in transplantation with regards to basic, translational and clinical research. Recent findings We describe new concepts in understanding allorecognition and allospecificity of T cells, and discuss current challenges in targeting memory T cells, including the limitation of rodent disease models. From a clinical perspective, we highlight the advances in molecular biopsy characterization, which have expanded our knowledge of potential drivers of injury and may provide better parameters for patient risk stratification. We also highlight the dual role of innate immunity in both stimulating and regulating adaptive immunity as well as novel insights into environmental exposures that may affect immune regulation, such as high-salt diet. Lastly, we discuss advances in understanding humoral response and novel technologies such as chimeric antigen receptors (CAR) engineered T cells, microparticle-based drug delivery and CRISPR/Cas9 gene editing that may provide intriguing and promising approaches to restrain alloimmunity. Summary Current advances in our understanding of the basic mechanisms of alloimmunity and their potential translation to clinical applications will permit the development of novel diagnostic and therapeutic strategies to improve long-term graft survival.

Cathepsin S and Protease-Activated Receptor-2 Drive Alloimmunity and Immune Regulation in Kidney Allograft Rejection

“…Presentation of alloantigen's is a central path mechanism of alloimmunity and involves MHC class II molecules on professional antigen-presenting cells (Borges et al, 2016;Robson et al, 2018). Within antigen-presenting cells, the maturation of MHC class II molecules is tightly regulated, whereby the invariant chain covers the peptide-binding domain up to when peptide loading occurs and the molecule is shuttled to the cell surface (Roche and Frusta, 2015;Robson et al, 2018).…”