Antigen-Presenting Cells: Potential of Proven und New Players in Immune Therapies

摘要

The immune system is permanently confronted with mutated and self-, microbe-, and tumor-derived neoantigens − as well as other, “unknown” antigens − and has to differentiate between self or nonself. These antigenic molecules (protein or lipid based) must be phagocytosed, processed, and/or presented in the respective major histocompatibility complex (MHC) molecules on the cell surface in recognizable form to train immune cells such as effector T cells, leading to their specific activation. These “trainers” are so-called antigen-presenting cells (APCs), which can be divided into professional (e.g., dendritic cells [DCs], B cells, and macrophages) and nonprofessional APCs (e.g., fibroblasts and hepatocytes). While all nucleated human cells can present peptide fragments of endogenous proteins using the MHC class I pathway and display them on the surface to CD8+ cytotoxic T lymphocytes [1, 2, 3], only professional APCs such as DCs, macrophages, and B cells are characterized by the ability to present exogenous antigens using MHC class II molecules and present them on MHC class II molecules to CD4+ T-helper cells (TH cells), along with the required costimulatory molecules, such as CD86 and CD83 molecules [2]. Therefore, the main difference between professional and nonprofessional APCs is the absence of MHC class II and costimulatory molecules on nonprofessional APCs. Recently, it was described that the three main granulocyte subsets (neutrophils, eosinophils, and basophils) also seem to be able to present exogenous antigens to naive TH cells via MHC class II molecules, which has led to the suggestion that they should be referred to as APCs [4, 5].