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Updated: May 15, 2026

Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
Published on: March 10, 2021
The adaptable major histocompatibility complex (MHC) fold: structure and function of nonclassical and MHC class
Erin J Adams1, Adrienne M Luoma
1Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA. ejadams@uchicago.edu
Abstract:
The MHC fold is found in proteins that have a range of functions in the maintenance of an organism's health, from immune regulation to fat metabolism. Well adapted for antigen presentation, as seen for peptides in the classical MHC molecules and for lipids in CD1 molecules, the MHC fold has also been modified to perform Fc-receptor activity (e.g., FcRn) and for roles in host homeostasis (e.g., with HFE and ZAG). The more divergent MHC-like molecules, such as some of those that interact with the NKG2D receptor, represent the minimal MHC fold, doing away with the α3 domain and β2m while maintaining the α1/α2 platform domain for receptor engagement. Viruses have also co-opted the MHC fold for immune-evasive functions. The variations on the theme of a β-sheet topped by two semiparallel α-helices are discussed in this review, highlighting the fantastic adaptability of this fold for good and for bad.
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