MHC I of the Great Reed Warbler Promotes a Flat Peptide Binding Mode

Area of Science:

• Immunology
• Structural Biology
• Avian Genetics

Background:

• The major histocompatibility complex (MHC) is crucial for adaptive immunity and pathogen recognition.
• Songbirds (Passeriformes) exhibit significantly higher MHC I gene copy numbers than other bird orders.
• Chicken (Gallus gallus) MHC I presents antigens with a bulging conformation, differing from typical antigen presentation.

Purpose of the Study:

• To investigate the structural basis of antigen presentation by MHC I in songbirds, a group with high MHC I gene diversity.
• To determine if MHC I in species with numerous genes presents antigens differently compared to species with fewer genes.

Main Methods:

• X-ray crystallography was employed to determine the three-dimensional structure of MHC I from the great reed warbler (Acrocephalus arundinaceus).
• Structural analysis focused on the peptide binding groove and its interaction with bound antigens.

Main Results:

• The X-ray structure of Acrocephalus arundinaceus MHC I (Acar3) revealed a unique, flat conformation for antigen binding.
• A conserved restriction point, formed by Arg97 and Arg155, acts like tweezers, holding the antigen in a flat orientation within the peptide binding groove.
• This stringent binding mechanism differs from the bulging presentation observed in chicken MHC I.

Conclusions:

• The flat antigen-binding conformation of songbird MHC I, mediated by specific residues, suggests a more constrained antigen presentation.
• This specialized antigen presentation mechanism may be a driving factor contributing to the high MHC I gene copy numbers observed in songbirds like the great reed warbler.