Summary
PDB 1KLG deposited: 2001-12-11 modified: 2009-02-24
Title Crystal structure of HLA-DR1/TPI(23-37, Thr28-->Ile mutant) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
Authors Andersen, P.S., Mariuzza, R.A., Sawicki, M.W., Sette, A., Southwood, S., Sundberg, E.J.
Method X-RAY DIFFRACTION
Structure factors resolution 2.4 rfactor 0.206 rfree 0.246
DPI 0.84 theoretical min: 0.31
Related PDB Entries 1KLU
Citations

While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies.

J Mol Biol. 2002 May 31;319(2):449-61.

Cross References
Database source Identifier Description
PubMed 12051920 JMOBAK
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1KLG/1 1KLG 1 tetramer 0 4 0 4899