7T5M

Structure of HLA-A*02:01-FLPTPEELGLLGPPRPQVLA complex

Summary for 7T5M

• Entry DOI: 10.2210/pdb7t5m/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Interleukin-27 receptor subunit alpha, ... (6 entities in total)
• Functional Keywords: hla, long epitope, 20mer, t cell recognition, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 92209.05

Authors

Gras, S. (deposition date: 2021-12-12, release date: 2022-12-14, Last modification date: 2024-10-23)

Primary citation

Meeuwsen, M.H.,Wouters, A.K.,Hagedoorn, R.S.,Kester, M.G.D.,Remst, D.F.G.,van der Steen, D.M.,de Ru, A.,van Veelen, P.A.,Rossjohn, J.,Gras, S.,Falkenburg, J.H.F.,Heemskerk, M.H.M.
Cutting Edge: Unconventional CD8 + T Cell Recognition of a Naturally Occurring HLA-A*02:01-Restricted 20mer Epitope.
J Immunol., 208:1851-1856, 2022

PubMed Abstract: Unconventional HLA class I-restricted CD8 T cell epitopes, longer than 10 aa, have been implicated to play a role in human immunity against viruses and cancer. T cell recognition of long peptides, centrally bulging from the HLA cleft, has been described previously. Alternatively, long peptides can contain a linear HLA-bound core peptide, with a N- or C-terminal peptide "tail" extending from the HLA peptide binding groove. The role of such a peptide "tail" in CD8 T cell recognition remains unclear. In this study, we identified a 20mer peptide (FLPTPEELGLLGPPRPQVLA [FLP]) derived from the IL-27R subunit α gene restricted to HLA-A*02:01, for which we solved the crystal structure and demonstrated a long C-terminal "tail" extension. FLP-specific T cell clones demonstrated various recognition modes, some T cells recognized the FLP core peptide, while for other T cells the peptide tail was essential for recognition. These results demonstrate a crucial role for a C-terminal peptide tail in immunogenicity.

PubMed: 35379743
DOI: 10.4049/jimmunol.2101208

Experimental method

X-RAY DIFFRACTION (1.67 Å)