Abstract
Major histocompatibility complex class I (MHC-I) molecules play a critical role in both innate and adaptive immune responses. The heterodimeric complex of a polymorphic MHC-I heavy chain and a conserved light chain binds to a diverse set of peptides which are presented at the cell surface. Peptide-free (empty) versions of MHC-I molecules are typically retained intracellularly due to their low stability and bound by endoplasmic reticulum chaperones and assembly factors. However, emerging evidence suggests that at least some MHC-I allotypes are relatively stable and detectable at the cell-surface as peptide-deficient conformers, under some conditions. Such MHC-I conformers interact with multiple immune receptors to mediate various immunological functions. Furthermore, conformational sensing of MHC-I molecules by intracellular assembly factors and endoplasmic reticulum chaperones influences the peptide repertoire, with profound consequences for immunity. In this review, we discuss recent advances relating to MHC-I conformational variations and their pathophysiological implications.