3KPR

Crystal Structure of the LC13 TCR in complex with HLA B*4405 bound to EEYLKAWTF a mimotope

Summary for 3KPR

• Entry DOI: 10.2210/pdb3kpr/pdb
• Related: 3KPL 3KPM 3KPN 3KPO 3KPP 3KPQ 3KPS
• Descriptor: HLA class I histocompatibility antigen, B-44 alpha chain, Beta-2-microglobulin, EEYLKAWTF, mimotope peptide, ... (6 entities in total)
• Functional Keywords: hla b*4405, tcrpmhc structure, ternary complex, allorecognition, tcr recognition, self peptide, disulfide bond, glycoprotein, host-virus interaction, immune response, membrane, mhc i, polymorphism, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30481; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 10
• Total formula weight: 188869.16

Authors

Macdonald, W.A.,Chen, Z.,Gras, S.,Archbold, J.K.,Tynan, F.E.,Clements, C.S.,Bharadwaj, M.,Kjer-Nielsen, L.,Saunders, P.M.,Wilce, M.C.,Crawford, F.,Stadinsky, B.,Jackson, D.,Brooks, A.G.,Purcell, A.W.,Kappler, J.W.,Burrows, S.R.,Rossjohn, J.,McCluskey, J. (deposition date: 2009-11-16, release date: 2009-12-22, Last modification date: 2024-11-06)

Primary citation

Macdonald, W.A.,Chen, Z.,Gras, S.,Archbold, J.K.,Tynan, F.E.,Clements, C.S.,Bharadwaj, M.,Kjer-Nielsen, L.,Saunders, P.M.,Wilce, M.C.,Crawford, F.,Stadinsky, B.,Jackson, D.,Brooks, A.G.,Purcell, A.W.,Kappler, J.W.,Burrows, S.R.,Rossjohn, J.,McCluskey, J.
T cell allorecognition via molecular mimicry.
Immunity, 31:897-908, 2009

PubMed Abstract: T cells often alloreact with foreign human leukocyte antigens (HLA). Here we showed the LC13 T cell receptor (TCR), selected for recognition on self-HLA-B( *)0801 bound to a viral peptide, alloreacts with B44 allotypes (HLA-B( *)4402 and HLA-B( *)4405) bound to two different allopeptides. Despite extensive polymorphism between HLA-B( *)0801, HLA-B( *)4402, and HLA-B( *)4405 and the disparate sequences of the viral and allopeptides, the LC13 TCR engaged these peptide-HLA (pHLA) complexes identically, accommodating mimicry of the viral peptide by the allopeptide. The viral and allopeptides adopted similar conformations only after TCR ligation, revealing an induced-fit mechanism of molecular mimicry. The LC13 T cells did not alloreact against HLA-B( *)4403, and the single residue polymorphism between HLA-B( *)4402 and HLA-B( *)4403 affected the plasticity of the allopeptide, revealing that molecular mimicry was associated with TCR specificity. Accordingly, molecular mimicry that is HLA and peptide dependent is a mechanism for human T cell alloreactivity between disparate cognate and allogeneic pHLA complexes.

PubMed: 20064448
DOI: 10.1016/j.immuni.2009.09.025

Experimental method

X-RAY DIFFRACTION (2.6 Å)