3MV9

Crystal Structure of the TK3-Gln55Ala TCR in complex with HLA-B*3501/HPVG

Summary for 3MV9

• Entry DOI: 10.2210/pdb3mv9/pdb
• Related: 2fyy 3MV7 3MV8
• Descriptor: HLA class I histocompatibility antigen, B-35 alpha chain, Beta-2-microglobulin, HPVG peptide from Epstein-Barr nuclear antigen 1, ... (7 entities in total)
• Functional Keywords: hla b*3501, ebv, tcr, tcrpmhc complex, hpvg, tcr polymorphism, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30685; Secreted: P61769; Host nucleus: P03211
• Total number of polymer chains: 5
• Total formula weight: 94552.57

Authors

Gras, S.,Chen, Z.,Miles, J.J.,Liu, Y.C.,Bell, M.J.,Sullivan, L.C.,Kjer-Nielsen, L.,Brennan, R.M.,Burrows, J.M.,Neller, M.A.,Khanna, R.,Purcell, A.W.,Brooks, A.G.,McCluskey, J.,Rossjohn, J.,Burrows, S.R. (deposition date: 2010-05-03, release date: 2010-06-09, Last modification date: 2024-10-30)

Primary citation

Gras, S.,Chen, Z.,Miles, J.J.,Liu, Y.C.,Bell, M.J.,Sullivan, L.C.,Kjer-Nielsen, L.,Brennan, R.M.,Burrows, J.M.,Neller, M.A.,Khanna, R.,Purcell, A.W.,Brooks, A.G.,McCluskey, J.,Rossjohn, J.,Burrows, S.R.
Allelic polymorphism in the T cell receptor and its impact on immune responses
J.Exp.Med., 207:1555-1567, 2010

PubMed Abstract: In comparison to human leukocyte antigen (HLA) polymorphism, the impact of allelic sequence variation within T cell receptor (TCR) loci is much less understood. Particular TCR loci have been associated with autoimmunity, but the molecular basis for this phenomenon is undefined. We examined the T cell response to an HLA-B*3501-restricted epitope (HPVGEADYFEY) from Epstein-Barr virus (EBV), which is frequently dominated by a TRBV9*01(+) public TCR (TK3). However, the common allelic variant TRBV9*02, which differs by a single amino acid near the CDR2beta loop (Gln55-->His55), was never used in this response. The structure of the TK3 TCR, its allelic variant, and a nonnaturally occurring mutant (Gln55-->Ala55) in complex with HLA-B*3501(HPVGEADYFEY) revealed that the Gln55-->His55 polymorphism affected the charge complementarity at the TCR-peptide-MHC interface, resulting in reduced functional recognition of the cognate and naturally occurring variants of this EBV peptide. Thus, polymorphism in the TCR loci may contribute toward variability in immune responses and the outcome of infection.

PubMed: 20566715
DOI: 10.1084/jem.20100603

Experimental method

X-RAY DIFFRACTION (2.7 Å)