3CZF

Crystal structure of HLA-B*2709 complexed with the glucagon receptor (GR) peptide (residues 412-420)

Summary for 3CZF

• Entry DOI: 10.2210/pdb3czf/pdb
• Related: 1of2 1uxw 2a83
• Descriptor: HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, BETA-2-MICROGLOBULIN, GLUCAGON RECEPTOR PEPTIDE, ... (5 entities in total)
• Functional Keywords: immune system, mhc (major histocompatibility complex, hla- b*2709
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 45534.56

Authors

Loll, B.,Fiorillo, M.T.,Rueckert, C.,Saenger, W.,Sorrentino, R.,Ziegler, A.,Uchanska-Ziegler, B. (deposition date: 2008-04-29, release date: 2009-04-07, Last modification date: 2024-11-06)

Primary citation

Loll, B.,Ruckert, C.,Uchanska-Ziegler, B.,Ziegler, A.
Conformational Plasticity of HLA-B27 Molecules Correlates Inversely With Efficiency of Negative T Cell Selection.
Front Immunol, 11:179-179, 2020

PubMed Abstract: The development of autoimmune disorders is incompletely understood. Inefficient thymic T cell selection against self-peptides presented by major histocompatibility antigens (HLA in humans) may contribute to the emergence of auto-reactive effector cells, and molecular mimicry between foreign and self-peptides could promote T cell cross-reactivity. A pair of class I subtypes, HLA-B2705 and HLA-B2709, have previously been intensely studied, because they are distinguished from each other only by a single amino acid exchange at the floor of the peptide-binding groove, yet are differentially associated with the autoinflammatory disorder ankylosing spondylitis. Using X-ray crystallography in combination with ensemble refinement, we find that the non-disease-associated subtype HLA-B2709, when presenting the self-peptide pGR (RRRWHRWRL), exhibits elevated conformational dynamics, and the complex can also be recognized by T cells. Both features are not observed in case of the sequence-related self-peptide pVIPR (RRKWRRWHL) in complex with this subtype, and T cell cross-reactivity between pGR, pVIPR, and the viral peptide pLMP2 (RRRWRRLTV) is only rarely observed. The disease-associated subtype HLA-B2705, however, exhibits extensive conformational flexibility in case of the three complexes, all of which are also recognized by frequently occurring cross-reactive T cells. A comparison of the structural and dynamic properties of the six HLA-B27 complexes, together with their individual ability to interact with T cells, permits us to correlate the flexibility of HLA-B27 complexes with effector cell reactivity. The results suggest the existence of an inverse relationship between conformational plasticity of peptide-HLA-B27 complexes and the efficiency of negative selection of self-reactive cells within the thymus.

PubMed: 32117305
DOI: 10.3389/fimmu.2020.00179

Experimental method

X-RAY DIFFRACTION (1.2 Å)