3MRC

Crystal Structure of MHC class I HLA-A2 molecule complexed with HCMV pp65-495-503 nonapeptide V6C variant

Summary for 3MRC

• Entry DOI: 10.2210/pdb3mrc/pdb
• Related: 3GSN 3GSO 3GSQ 3GSR 3GSU 3GSV 3GSW 3GSX 3MR9 3MRB 3MRD 3MRE 3MRF 3MRG 3MRH 3MRI 3MRJ 3MRK 3MRL 3MRM 3MRN 3MRO 3MRP 3MRQ 3MRR
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, 9-meric peptide from Tegument protein pp65, ... (4 entities in total)
• Functional Keywords: mhc class i, hla, immune system, immune response, nonapeptide, viral peptide, cytomegalovirus, pp65 protein
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted : P61769; Virion tegument : Q6SW59
• Total number of polymer chains: 3
• Total formula weight: 44805.89

Authors

Gras, S.,Reiser, J.-B.,Chouquet, A.,Debeaupuis, E.,Echasserieau, K.,Saulquin, X.,Bonneville, M.,Housset, D. (deposition date: 2010-04-29, release date: 2011-05-25, Last modification date: 2024-10-09)

Primary citation

Reiser, J.B.,Legoux, F.,Gras, S.,Trudel, E.,Chouquet, A.,Leger, A.,Le Gorrec, M.,Machillot, P.,Bonneville, M.,Saulquin, X.,Housset, D.
Analysis of Relationships between Peptide/MHC Structural Features and Naive T Cell Frequency in Humans.
J.Immunol., 193:5816-5826, 2014

PubMed Abstract: The structural rules governing peptide/MHC (pMHC) recognition by T cells remain unclear. To address this question, we performed a structural characterization of several HLA-A2/peptide complexes and assessed in parallel their antigenicity, by analyzing the frequency of the corresponding Ag-specific naive T cells in A2(+) and A2(-) individuals, as well as within CD4(+) and CD8(+) subsets. We were able to find a correlation between specific naive T cell frequency and peptide solvent accessibility and/or mobility for a subset of moderately prominent peptides. However, one single structural parameter of the pMHC complexes could not be identified to explain each peptide antigenicity. Enhanced pMHC antigenicity was associated with both highly biased TRAV usage, possibly reflecting favored interaction between particular pMHC complexes and germline TRAV loops, and peptide structural features allowing interactions with a broad range of permissive CDR3 loops. In this context of constrained TCR docking mode, an optimal peptide solvent exposed surface leading to an optimal complementarity with TCR interface may constitute one of the key features leading to high frequency of specific T cells. Altogether our results suggest that frequency of specific T cells depends on the fine-tuning of several parameters, the structural determinants governing TCR-pMHC interaction being just one of them.

PubMed: 25392532
DOI: 10.4049/jimmunol.1303084

Experimental method

X-RAY DIFFRACTION (1.8 Å)