3UTS

1E6-A*0201-ALWGPDPAAA Complex, Monoclinic

Summary for 3UTS

• Entry DOI: 10.2210/pdb3uts/pdb
• Related: 3UTP 3UTQ 3UTT
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Insulin, ... (8 entities in total)
• Functional Keywords: major histocompatibility complex, human leukocyte antigen, type i diabetes, t cell receptor, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769 P01308
• Total number of polymer chains: 10
• Total formula weight: 191256.75

Authors

Rizkallah, P.J.,Cole, D.K.,Sewell, A.K.,Bulek, A.M. (deposition date: 2011-11-26, release date: 2012-01-25, Last modification date: 2024-11-20)

Primary citation

Bulek, A.M.,Cole, D.K.,Skowera, A.,Dolton, G.,Gras, S.,Madura, F.,Fuller, A.,Miles, J.J.,Gostick, E.,Price, D.A.,Drijfhout, J.W.,Knight, R.R.,Huang, G.C.,Lissin, N.,Molloy, P.E.,Wooldridge, L.,Jakobsen, B.K.,Rossjohn, J.,Peakman, M.,Rizkallah, P.J.,Sewell, A.K.
Structural basis for the killing of human beta cells by CD8(+) T cells in type 1 diabetes.
Nat.Immunol., 13:283-289, 2012

PubMed Abstract: The structural characteristics of the engagement of major histocompatibility complex (MHC) class II-restricted self antigens by autoreactive T cell antigen receptors (TCRs) is established, but how autoimmune TCRs interact with complexes of self peptide and MHC class I has been unclear. Here we examined how CD8(+) T cells kill human islet beta cells in type 1 diabetes via recognition of a human leukocyte antigen HLA-A*0201-restricted glucose-sensitive preproinsulin peptide by the autoreactive TCR 1E6. Rigid 'lock-and-key' binding underpinned the 1E6-HLA-A*0201-peptide interaction, whereby 1E6 docked similarly to most MHC class I-restricted TCRs. However, this interaction was extraordinarily weak because of limited contacts with MHC class I. TCR binding was highly peptide centric, dominated by two residues of the complementarity-determining region 3 (CDR3) loops that acted as an 'aromatic-cap' over the complex of peptide and MHC class I (pMHCI). Thus, highly focused peptide-centric interactions associated with suboptimal TCR-pMHCI binding affinities might lead to thymic escape and potential CD8(+) T cell-mediated autoreactivity.

PubMed: 22245737
DOI: 10.1038/ni.2206

Experimental method

X-RAY DIFFRACTION (2.712 Å)