43RH

Crystal structure of TCR C3K in complex with H2-Q9/VP2.139

Summary for 43RH

• Entry DOI: 10.2210/pdb43rh/pdb
• Descriptor: Histocompatibility 2, Q region locus 7, Beta-2-microglobulin, T cell receptor alpha variable 13D-1,T cell receptor alpha joining 18,T cell receptor alpha chain constant, ... (7 entities in total)
• Functional Keywords: complex, tcr, mhc, viral, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 7
• Total formula weight: 144540.00

Authors

Tennant, L.,Jobichen, C.,Tran, M.T.,Littler, D.R.,Farenc, C.,Gras, S.,Lukacher, A.E.,Sullivan, L.C.,Brooks, A.G.,Rossjohn, J. (deposition date: 2026-07-14, release date: 2026-07-29, Last modification date: 2026-09-30)

Primary citation

Tennant, L.,Jobichen, C.,Tran, M.T.,Farenc, C.,Gras, S.,Lukacher, A.E.,Sullivan, L.C.,Brooks, A.G.,Rossjohn, J.
A murine MHC-Ib molecule, H2-Q9, drives peptide-centric T cell receptor recognition of a viral antigen.
J.Biol.Chem., :113574-113574, 2026

PubMed Abstract: Highly polymorphic classical major histocompatibility complex class I (MHC-Ia) molecules present peptides to T cell receptors (TCRs) expressed on CD8 T cells. In contrast, non-classical MHC-Ib molecules are less polymorphic, and the structural principles governing their recognition by TCRs remains poorly understood. H2-Q9, a murine Qa-2 family MHC-Ib molecule presents the mouse polyomavirus-derived VP2.139 peptide (HALNVVHDW) to CD8 T cells, yet the molecular basis of TCR recognition of H2-Q9/peptide complexes remains unclear. Here, we characterised the interactions of two VP2.139-specific TCRs, C3K and AH1, with the VP2.139 peptide presented by H2-Q9, which showed similar moderate binding affinities. We then determined the structure of the TCR C3K bound to the VP2.139 peptide presented by H2-Q9. TCR C3K adopted a diagonal docking orientation and was tilted toward the N-terminal end of the peptide. The CDR3 loops formed extensive contacts with peptide positions P1-P8, whereas alanine-scanning mutagenesis at positions P1-P7 impaired TCR recognition. Structural comparison of H2-Q9 with classical murine MHC-Ia molecules identified substitutions in the α3-domain that alter the CD8-binding interface and may explain the previously observed absence of CD8 binding to H2-Q9. Together, these findings provide insight into antigen recognition by a monomorphic MHC-Ib molecule.

PubMed: 42754157
DOI: 10.1016/j.jbc.2026.113574

Experimental method

X-RAY DIFFRACTION (3.33 Å)