Figure 1.

Structure of CD8 isoforms and placement within the immunological synapse with potential strategies for immunomodulation. (A) Crystal structure of mouse CD8αα ectodomain (PDB ID 1BQH). (B) Crystal structure of mouse CD8αβ ectodomain (PDB ID 2ATP). (C) Overlay of mouse CD8αα with mouse CD8αβ ectodomain. (D) Molecular model of the immunological synapse derived from the cryo-EM structure of the MHC-I/TCR/CD3 complex (PDB ID 7PHR) aligned to mouse CD8αα/H-2K^b (PDB ID 1BQH). The complex was adapted from a model presented by Pandey et al. (56). MHC-I heavy chain is colored green, β2m light chain colored cyan, peptide antigen colored salmon, CD8α colored magenta, CD8β colored yellow, TCR chains colored orange, and CD3 chains colored brown. Potential mechanisms for immunomodulation of CD8 structure/interactions by mABs (described in detail in the text) are highlighted with blue text/dotted arrows.