8SHI

Valpha3S1 Vbeta13S1 HLA C 0602 VRSRRCLRL

Summary for 8SHI

• Entry DOI: 10.2210/pdb8shi/pdb
• Descriptor: MHC class I antigen (Fragment), Beta-2-microglobulin, VAL-ARG-SER-ARG-ARG-ABA-LEU-ARG-LEU, ... (6 entities in total)
• Functional Keywords: complex, t cell receptor, psoriasis, tcr hla-c, hla-c6:02, adamstl5, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 188026.13

Authors

Littler, D.R.,Anand, S.,Vivian, J.P.,Rossjohn, J. (deposition date: 2023-04-14, release date: 2023-06-28, Last modification date: 2023-07-26)

Primary citation

Anand, S.,Littler, D.R.,Mobbs, J.I.,Braun, A.,Baker, D.G.,Tennant, L.,Purcell, A.W.,Vivian, J.P.,Rossjohn, J.
Complimentary electrostatics dominate T-cell receptor binding to a psoriasis-associated peptide antigen presented by human leukocyte antigen C∗06:02.
J.Biol.Chem., 299:104930-104930, 2023

PubMed Abstract: Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the human leukocyte antigen (HLA) C∗06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Vα3S1/Vβ13S1) isolated from psoriatic plaques is selective for HLA-C∗06:02, presenting a peptide derived from the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR-HLA-C∗06:02 ADAMTSL5 complex with a stabilized peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C∗06:02 α1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide-binding groove of HLA-C∗06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding the engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis while simultaneously expanding our knowledge of how TCRs engage HLA-C.

PubMed: 37330172
DOI: 10.1016/j.jbc.2023.104930

Experimental method

X-RAY DIFFRACTION (2.90001719663 Å)