Figure 1.

The antigen presenting role of MHC class I molecules and their structure. (A) The immunological synapse is a communication platform between a (professional) antigen-presenting cell and a T or NK cell. In the example presented here, MHC-I molecules on the surface of a dendritic cell (purple) present antigens (orange) for their recognition by the TCR of a CD8⁺ T cell (blue). CD8 acts as co-receptor of the TCR for the recognition of the MHC-I molecule. At the immunological synapse (red box), other molecules required for the engagement and modulation of the interaction are also recruited, such as adhesion molecules (LFA-1 and ICAM-I) and costimulatory molecules (CD80/86 and CD28). (B) MHC-I molecules are heterodimers composed of a heavy α chain (blue) and a light chain (β2-microglobulin) (gray). Most α chains are made up of two peptide binding domains (α1 and α2), and an Ig-like α3 domain recognized by CD8 molecules on T cells. Additionally, the α chain has a transmembrane and a short cytoplasmic tail (cyan). (C) The cytoplasmic regions of several classical and non-classical MHC-I α chains contain a tyrosine residue that can be phosphorylated. This phospho-tyrosine residue has been proposed to interact with signaling proteins and thus leads to reverse signaling. Here we present the cytoplasmic regions of human classical (MHC-Ia) and non-classical (MHC-Ib) α chains, and the classical mouse α chains. However, some of the multiple non-classical mouse α chains also contain this tyrosine residue.