Simplifying principles underlying the highly complex peptide motif of the promiscuous chicken MHC class I molecule, BF2*21:01
14 affiliations
- 1Department of Pathology, University of Cambridge, Cambridge, United Kingdom
- 2University of Oxford, Sir William Dunn School of Pathology, Oxford, United Kingdom
- 3University of Edinburgh, Institute for Immunology and Infection Research, Edinburgh, United Kingdom
- 4Department of Biochemistry, University of Cambridge, Cambridge Centre for Proteomics, Cambridge, United Kingdom
- 5Basel Institute for Immunology, Basel, Switzerland
- 6Institute for Animal Health, Compton, United Kingdom
- 7Pirbright Institute, Pirbright, United Kingdom
- 8Department of Biology, University of Oxford, Oxford, United Kingdom
- 9Department of Structural Biology, St Jude Children's Research Hospital, Memphis, United States
- 10University of Oxford, Centre for Immuno-Oncology, Old Road Campus, Headington, United Kingdom
- 11University of Oxford, Jenner Institute, Old Road Campus, Headington, United Kingdom
- 12University of Dundee, School of Life Sciences, Dundee, United Kingdom
- 13Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
- 14Department of Immunobiology, Yale University, New Haven, United States
Abstract
In chickens and humans, classical class I molecules of the major histocompatibility complex (MHC) have a spectrum of correlated properties, including cell surface expression and peptide repertoire. Understanding the impact of these promiscuous generalists and fastidious specialists is of considerable interest. The promiscuous BF2 molecule from the chicken B21 haplotype, BF2*21:01, binds a wide range of peptides by remodelling the peptide-binding site, allowing co-variation of the anchor residues at peptide positions P₂ and Pc-2, and binding of an anchor residue at Pc. Using in vitro refolding assays with peptides and peptide libraries, determining thermostability and crystal structures, and analysing a chicken B21 cell line by immunopeptidomics, we found that BF2*21:01 will accommodate many possible combinations at P₂ and Pc-2, as well as several hydrophobic amino acids at Pc. However, marked preferences for particular peptide lengths, particular amino acids at the three anchor residues, and particular combinations of amino acids at P₂ and Pc-2 as well as at P₃ and Pc-3 together lead to high frequencies of major peptides while still allowing the possibility of presenting a wide peptide repertoire. These simplifying principles may eventually allow predictions of pathogen peptides with stable binding for this iconic promiscuous class I molecule, as well as providing the data for more sophisticated peptide prediction methods.
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BibTeX
@article{harrison2026simplifying,
title = {{Simplifying principles underlying the highly complex peptide motif of the promiscuous chicken MHC class I molecule, BF2*21:01}},
author = {Michael Harrison and Paul E Chappell and Samer Halabi and Maria Danysz and Enock M Mararo and Lukasz Magiera and Clemens Hermann and Michael J Deery and Kathryn S Lilley and Hans-Joachim Wallny and David W Avila and William Mwangi and Venugopal Nair and Susan M Lea and Nicola Ternette and Jim Kaufman},
journal = {eLife},
year = {2026},
month = nov,
doi = {10.7554/elife.111098},
url = {https://elifesciences.org/articles/111098},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Simplifying principles underlying the highly complex peptide motif of the promiscuous chicken MHC class I molecule, BF2*21:01
AU - Michael Harrison
AU - Paul E Chappell
AU - Samer Halabi
AU - Maria Danysz
AU - Enock M Mararo
AU - Lukasz Magiera
AU - Clemens Hermann
AU - Michael J Deery
AU - Kathryn S Lilley
AU - Hans-Joachim Wallny
AU - David W Avila
AU - William Mwangi
AU - Venugopal Nair
AU - Susan M Lea
AU - Nicola Ternette
AU - Jim Kaufman
PY - 2026
DA - 2026/11/02
JO - eLife
DO - 10.7554/elife.111098
UR - https://elifesciences.org/articles/111098
AB - In chickens and humans, classical class I molecules of the major histocompatibility complex (MHC) have a spectrum of correlated properties, including cell surface expression and peptide repertoire. Understanding the impact of these promiscuous generalists and fastidious specialists is of considerable interest. The promiscuous BF2 molecule from the chicken B21 haplotype, BF2*21:01, binds a wide range of peptides by remodelling the peptide-binding site, allowing co-variation of the anchor residues at peptide positions P₂ and Pc-2, and binding of an anchor residue at Pc. Using in vitro refolding assays with peptides and peptide libraries, determining thermostability and crystal structures, and analysing a chicken B21 cell line by immunopeptidomics, we found that BF2*21:01 will accommodate many possible combinations at P₂ and Pc-2, as well as several hydrophobic amino acids at Pc. However, marked preferences for particular peptide lengths, particular amino acids at the three anchor residues, and particular combinations of amino acids at P₂ and Pc-2 as well as at P₃ and Pc-3 together lead to high frequencies of major peptides while still allowing the possibility of presenting a wide peptide repertoire. These simplifying principles may eventually allow predictions of pathogen peptides with stable binding for this iconic promiscuous class I molecule, as well as providing the data for more sophisticated peptide prediction methods.
SN - 2050-084X
ER -