9AUD

Immune receptor complex

Summary for 9AUD

• Entry DOI: 10.2210/pdb9aud/pdb
• Related: 8VQ8
• Descriptor: H-2 class II histocompatibility antigen, A-B alpha chain, Nucleoprotein,H-2 class II histocompatibility antigen, A beta chain, NPLCK1-2_TCR TRAV6-5 alpha chain, ... (7 entities in total)
• Functional Keywords: peptide hla complex, immune system-viral peptide complex, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 4
• Total formula weight: 99136.40

Authors

Chaurasia, P.,Littler, D.R.,La Gruta, N.,Rossjohn, J. (deposition date: 2024-02-29, release date: 2025-02-05, Last modification date: 2025-08-13)

Primary citation

Zhang, J.B.,Chaurasia, P.,Nguyen, A.,Huang, Z.,Nguyen, T.T.,Xu, H.,Tran, M.T.,Reid, H.H.,Jones, C.M.,Schattgen, S.A.,Thiele, D.,Thomas, P.G.,Rientjes, J.,Good-Jacobson, K.L.,Ruscher, R.,Littler, D.R.,Rossjohn, J.,Zareie, P.,La Gruta, N.L.
LCK-co-receptor association ensures T cell lineage fidelity and maximizes epitope-specific TCR diversity.
Sci Immunol, 10:eadp5016-eadp5016, 2025

PubMed Abstract: The interaction between the CD4/CD8 co-receptors and LCK (an Src family tyrosine kinase) is thought to augment T cell activation upon recognition of peptide-loaded major histocompatibility complexes (pMHCs). How this interaction influences antigen-specific T cell development is unclear however, as is its impact on naïve and immune antigen-specific T cell repertoires. In mice expressing mutated endogenous LCK unable to bind co-receptors (LCK mice), we show that influenza A virus (IAV)-derived pMHC-specific CD8 and CD4 T cell responses had a significantly narrowed T cell receptor (TCR) repertoire, favoring high-affinity TCRs. This narrowing was established during T cell development and was exacerbated after viral infection. The dissociation of LCK from co-receptors also resulted in the redirection of CD4-fated T cells to the CD8 lineage, with expanded pMHCII-specific cytotoxic CD8 T cells observed after IAV infection. Thus, LCK-co-receptor association is critical for ensuring T cell lineage fidelity and maximizing antigen-specific T cell repertoire diversity.

PubMed: 39982976
DOI: 10.1126/sciimmunol.adp5016

Experimental method

X-RAY DIFFRACTION (2.9 Å)