7N6D

HLA peptide complex

Summary for 7N6D

• Entry DOI: 10.2210/pdb7n6d/pdb
• Related: 7N6E
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Spike protein S1, ... (5 entities in total)
• Functional Keywords: peptide hla complex, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 181679.98

Authors

Chaurasia, P.,Petersen, J.,Rossjohn, J. (deposition date: 2021-06-08, release date: 2021-07-28, Last modification date: 2024-10-16)

Primary citation

Chaurasia, P.,Nguyen, T.H.O.,Rowntree, L.C.,Juno, J.A.,Wheatley, A.K.,Kent, S.J.,Kedzierska, K.,Rossjohn, J.,Petersen, J.
Structural basis of biased T cell receptor recognition of an immunodominant HLA-A2 epitope of the SARS-CoV-2 spike protein.
J.Biol.Chem., 297:101065-101065, 2021

PubMed Abstract: CD8 T cells play an important role in vaccination and immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although numerous SARS-CoV-2 CD8 T cell epitopes have been identified, the molecular basis underpinning T cell receptor (TCR) recognition of SARS-CoV-2-specific T cells remains unknown. The T cell response directed toward SARS-CoV-2 spike protein-derived S peptide presented by the human leukocyte antigen (HLA)-A∗02:01 allomorph (hereafter the HLA-A2 epitope) is, to date, the most immunodominant SARS-CoV-2 epitope found in individuals bearing this allele. As HLA-A2-specific CD8 T cells utilize biased TRAV12 gene usage within the TCR α-chain, we sought to understand the molecular basis underpinning this TRAV12 dominance. We expressed four TRAV12 TCRs which bound the HLA-A2 complex with low micromolar affinity and determined the crystal structure of the HLA-A2 binary complex, and subsequently a ternary structure of the TRAV12 TCR complexed to HLA-A2. We found that the TCR made extensive contacts along the entire length of the S peptide, suggesting that the TRAV12 TCRs would be sensitive to sequence variation within this epitope. To examine this, we investigated cross-reactivity toward analogous peptides from existing SARS-CoV-2 variants and closely related coronaviruses. We show via surface plasmon resonance and tetramer studies that the TRAV12 T cell repertoire cross-reacts poorly with these analogous epitopes. Overall, we defined the structural basis underpinning biased TCR recognition of CD8 T cells directed at an immunodominant epitope and provide a framework for understanding TCR cross-reactivity toward viral variants within the S peptide.

PubMed: 34384783
DOI: 10.1016/j.jbc.2021.101065

Experimental method

X-RAY DIFFRACTION (2.3 Å)