4Y1A

immune complex

Summary for 4Y1A

• Entry DOI: 10.2210/pdb4y1a/pdb
• Related: 4Y19
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-4 beta chain, Insulin, ... (6 entities in total)
• Functional Keywords: tcr mhc, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 97058.35

Authors

Beringer, D.X.,Vivian, J.P.,Reid, H.H.,Rossjohn, J. (deposition date: 2015-02-07, release date: 2015-09-23, Last modification date: 2024-10-30)

Primary citation

Beringer, D.X.,Kleijwegt, F.S.,Wiede, F.,van der Slik, A.R.,Loh, K.L.,Petersen, J.,Dudek, N.L.,Duinkerken, G.,Laban, S.,Joosten, A.,Vivian, J.P.,Chen, Z.,Uldrich, A.P.,Godfrey, D.I.,McCluskey, J.,Price, D.A.,Radford, K.J.,Purcell, A.W.,Nikolic, T.,Reid, H.H.,Tiganis, T.,Roep, B.O.,Rossjohn, J.
T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex.
Nat.Immunol., 16:1153-1161, 2015

PubMed Abstract: Central to adaptive immunity is the interaction between the αβ T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 180° polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iT(reg) TCR α-chain and β-chain are overlaid with the α-chain and β-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.

PubMed: 26437244
DOI: 10.1038/ni.3271

Experimental method

X-RAY DIFFRACTION (4 Å)