7T2A

Crystal structure of HLA-DP4 in complex with Ply

Summary for 7T2A

• Entry DOI: 10.2210/pdb7t2a/pdb
• Descriptor: HLA class II histocompatibility antigen, DP alpha 1 chain, HLA class II histocompatibility antigen, DP beta 1 chain, Pneumolysin-derived peptide, ... (4 entities in total)
• Functional Keywords: phla complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 90256.63

Authors

Ciacchi, L.,Farenc, C.,Petersen, J.,Reid, H.H.,Rossjohn, J. (deposition date: 2021-12-03, release date: 2022-12-28, Last modification date: 2023-10-25)

Primary citation

Ciacchi, L.,van de Garde, M.D.B.,Ladell, K.,Farenc, C.,Poelen, M.C.M.,Miners, K.L.,Llerena, C.,Reid, H.H.,Petersen, J.,Price, D.A.,Rossjohn, J.,van Els, C.A.C.M.
CD4 + T cell-mediated recognition of a conserved cholesterol-dependent cytolysin epitope generates broad antibacterial immunity.
Immunity, 56:1082-1097.e6, 2023

PubMed Abstract: CD4 T cell-mediated immunity against Streptococcus pneumoniae (pneumococcus) can protect against recurrent bacterial colonization and invasive pneumococcal diseases (IPDs). Although such immune responses are common, the pertinent antigens have remained elusive. We identified an immunodominant CD4 T cell epitope derived from pneumolysin (Ply), a member of the bacterial cholesterol-dependent cytolysins (CDCs). This epitope was broadly immunogenic as a consequence of presentation by the pervasive human leukocyte antigen (HLA) allotypes DPB102 and DPB104 and recognition via architecturally diverse T cell receptors (TCRs). Moreover, the immunogenicity of Ply was underpinned by core residues in the conserved undecapeptide region (ECTGLAWEWWR), enabling cross-recognition of heterologous bacterial pathogens expressing CDCs. Molecular studies further showed that HLA-DP4-Ply was engaged similarly by private and public TCRs. Collectively, these findings reveal the mechanistic determinants of near-global immune focusing on a trans-phyla bacterial epitope, which could inform ancillary strategies to combat various life-threatening infectious diseases, including IPDs.

PubMed: 37100059
DOI: 10.1016/j.immuni.2023.03.020

Experimental method

X-RAY DIFFRACTION (3.04 Å)