3KWW: Crystal structure of the 'restriction triad' mutant of HLA B*3508, beta-2-microglobulin and EBV peptide

alphabeta T cell receptors (TCRs) are genetically restricted to corecognize peptide antigens bound to self-major histocompatibility complex (pMHC) molecules; however, the basis for this MHC specificity remains unclear. Despite the current dogma, evaluation of the TCR-pMHC-I structural database shows that the nongermline-encoded complementarity-determining region (CDR)-3 loops often contact the MHC-I, and the germline-encoded CDR1 and -2 loops frequently participate in peptide-mediated interactions. Nevertheless, different TCRs adopt a roughly conserved docking mode over the pMHC-I, in which three MHC-I residues (65, 69, and 155) are invariably contacted by the TCR in one way or another. Nonetheless, the impact of mutations at these three positions, either individually or together, was not uniformly detrimental to TCR recognition of pHLA-B*0801 or pHLA-B*3508. Moreover, when TCR-pMHC-I recognition was impaired, this could be partially restored by expression of the CD8 coreceptor. The structure of a TCR-pMHC-I complex in which these three (65, 69, and 155) MHC-I positions were all mutated resulted in shifting of the TCR footprint relative to the cognate complex and formation of compensatory interactions. Collectively, our findings reveal the inherent adaptability of the TCR in maintaining peptide recognition while accommodating changes to the central docking site on the pMHC-I.
PDB ID: 3KWWDownload
MMDB ID: 82622
PDB Deposition Date: 2009/12/1
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.18  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 3KWW: trimeric; determined by author and by software (PISA)
Molecular Components in 3KWW
Label Count Molecule
Proteins (3 molecules)
HLA Class I Histocompatibility Antigen, B-35 Alpha Chain(Gene symbol: HLA-B)
Molecule annotation
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
Peptide From Trans-activator Protein Bzlf1
Molecule annotation
Chemicals (16 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB