Chapter 6: Antigen Presentation to T Lymphocytes the basis for activation. Among these activating antigens is Skint-1 (selection and upkeep of intraepithelial T cells 1), an immunoglobulin superfamily member that is expressed by thymic epithelial cells and by keratinocytes. Skint-1 seems to be required for the generation of a subset of Vγ5:Vδ1 T cells that develop in the thymus and home to the skin to become ‘dendritic epidermal T cells’ (DETCs). Some evidence suggests a direct interaction between Skint-1 and the γ:δ T-cell receptor, although structural studies are not yet available. Conceivably, DETCs localize to the skin due to recognition by their T-cell receptor of Skint-1 expressed by keratinocytes. There, they might provide a ‘transitional’ mode of immune defense, becoming activated through innate receptors that are triggered locally during infections.
Summary.
Antigen presentation to various nonconventional T-cell subsets and γ:δT cells generally does not involve the generation of peptide:MHC complexes. Instead, these cells recognize surface proteins, such as ULBPs and RAET-1 proteins, that may indicate cellular stress, transformation, or intracellular infection, or nonpeptide antigens, such as microbial glycolipids or folate metabolites presented by CD1 molecules. The MHC region contains many genes whose structure is closely related to the MHC class I molecules—the so-called non-classical, or class Ib, MHC. Some of these genes serve purposes that are unrelated to the immune system, but many are involved in recognition by activating and inhibitory receptors expressed by NK cells, γ:δ T cells, and α:β T cells. MHC class Ib proteins called CD1 molecules are encoded outside the MHC region. CD1c and CD1d can bind lipids and glycolipid antigens for presentation to iNKT cells expressing invariant T-cell receptors. The T-cell population called MAIT cells, which are abundant in humans, recognize vitamin B9 metabolites presented by the MR1 MHC class Ib molecule, suggesting that the MAIT cells have a ‘transitional’ role between innate and adaptive immunity. Likewise, many antigens that activate γ:δ T cells may be indicators of stress or infection, and these cells are able to generate cytokines that amplify immune defense pathways.
Summary to Chapter 6.
T-cell receptors on conventional α:β T cells recognize peptides bound to MHC molecules. In the absence of infection, MHC molecules are occupied by self peptides, which do not normally provoke a T-cell response, because of various tolerance mechanisms. But during infections, pathogen-derived peptides become bound to MHC molecules and are displayed on the cell surface, where they can be recognized by T cells that have been previously activated and armed for the specific peptide:MHC complex. Naive T cells become activated when they encounter their specific antigen presented on activated dendritic cells. MHC class I molecules in most cells bind to peptides derived from proteins that have been synthesized and then degraded in the cytosol. Some dendritic cells can obtain and process exogenous antigens and present them on MHC class I molecules. This process of cross-presentation is important for priming CD8 T cells to many viral infections.