MHC-Class II Molecules

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Human γδ T cells are considered professional antigen-presenting cells (APCs) because they can express MHC class II molecules, costimulatory molecules, and lymph node homing chemokine receptors.

Introduction of MHC-class II Molecules

MHC-class II molecules are a major class of histocompatibility complex (MHC) molecules, which are usually found only in specialized APCs, such as dendritic cells, monocytes, certain endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating the immune response. Like MHC class I molecules, class II molecules are also heterodimers, which consist of two homologous peptides (α and β chains) encoded by MHC. Since the binding slots of MHC class II molecules are open at both ends, the antigens presented by MHC class II molecules are longer, usually 15 to 24 amino acid residues.

Overview of MHC-class II antigen presentation pathway. Fig.1 Overview of MHC-class II antigen presentation pathway. (Wosen, 2018)

MHC-class II Molecules Recognition by γδ T Cells

Studies have shown that activated Vδ2 T cells express cell adhesion molecules, including CD86, CD80, and MHC-II, which display the characteristics of professional APCs. Vγ9Vδ2 T cells have the unique characteristics of recognizing non-peptide phosphorylated antigens. These cells react strongly in vitro to the stimulation of microorganisms or synthetic phosphoantigens. They play a vital role in anti-infection immunity and anti-tumor surveillance.

MHC-class II alleles are the main genetic factor of susceptibility to many autoimmune diseases. MHC-class II molecules are constitutively expressed on dendritic cells, B cells, and monocytes, but can be induced to express on mesenchymal and epithelial cells under inflammatory conditions. The genetic background of the host, especially the alleles of MHC-class II (IA or IE for mice; HLA-DR, -DP or -DQ for humans), can affect the cytokine bias (immune deviation) of T cell response to antigenic stimulus in vivo, as demonstrated in several autoimmune disease mouse system.

Rheumatoid rescue of misfolded proteins by MHC-class II molecules. Fig.2 Rheumatoid rescue of misfolded proteins by MHC-class II molecules. (Hisashi, 2016)

Previous studies have demonstrated that γδ T MHC-II can present and cross-present antigens from soluble proteins, and also confirmed that γδ T cells in human blood can take up large fragments from intact cells through the process of phagocytosis or trogocytosis. In addition, the antigens associated with these large (>1 μm) structures can be processed by γδ T cells and presented to other T cells. Therefore, when activated γδ T cells are co-cultured with transformed cells, tumor cells can not only serve as targets for γδ T-mediated killing but also as a source of tumor-associated antigens, which are expressed from γδ T cells to tumor-reactive αβ T cells.


  1. Wosen, J. E., et al. Epithelial MHC Class II Expression and Its Role in Antigen Presentation in the Gastrointestinal and Respiratory Tracts. Frontiers in Immunology. 2018, 9.
  2. Hisashi, A. Rheumatoid Rescue of Misfolded Cellular Proteins by MHC Class II Molecules: A New Hypothesis for Autoimmune Diseases. Advances in Immunology. 2016, 129.
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