Molecular basis for presentation of N-myristoylated peptides by the chicken YF1*7.1 molecule.

Khandokar, Yogesh, Cheng, Tan Yun, Wang, Carl J. H., Cao, Thinh-Phat, Nagampalli, Raghavendra S. K., Sivaraman, Komagal Kannan, Van Rhijn, Ildiko, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Moody, D. Branch and Le Nours, Jérôme 2025. Molecular basis for presentation of N-myristoylated peptides by the chicken YF1*7.1 molecule. Journal of Biological Chemistry , 110253. 10.1016/j.jbc.2025.110253

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Abstract

Major Histocompatibility Complex I (MHC-I) and MHC-I-like molecules play a central role in mediating immunity. Through their conservation across all taxa of jawed vertebrates, the MHC-I-like proteins have adapted to present non-peptidic antigens to distinct T cell populations. While our understanding of the structure-function relationship of MHC-I and MHC-I-like molecules in humans and mice is well established, the nature of the antigens presented by MHC-I- like molecules in 'non-model' species remains unclear. Here, using a mammalian recombinant expression system combined with mass spectrometry approaches, we identified N-myristoylated peptides as endogenous ligands for the chicken MHC-I-like protein YF1*7.1. Given the importance of N-myristoylation in viral pathogenesis, we determined the crystal structure of YF1*7.1 in complex with two N-myristoylated peptides derived from Marek's disease virus (MDV), demonstrating the molecular basis that underpins the presentation of N-myristoylated peptides from MDV, a highly contagious and fatal viral neoplastic disease in chickens. Thus, the identified ligands are distinct from unmodified peptides found in classical MHC-I and -II as well as diverse amphipathic lipids captured by CD1 proteins. Collectively, our study lays the foundation for further molecular and functional characterization of YF1*7.1 and more broadly of the role of the MHC-I encoded by the MHC-Y gene cluster in protection against highly contagious viral neoplastic diseases in chickens. [Abstract copyright: Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.]

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Elsevier
ISSN:	0021-9258
Date of First Compliant Deposit:	9 June 2025
Date of Acceptance:	26 April 2025
Last Modified:	09 Jun 2025 14:45
URI:	https://orca.cardiff.ac.uk/id/eprint/178931

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