1klg
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Crystal structure of HLA-DR1/TPI(23-37, Thr28-->Ile mutant) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
OverviewOverview
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.
About this StructureAbout this Structure
1KLG is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA.
ReferenceReference
Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line., Sundberg EJ, Sawicki MW, Southwood S, Andersen PS, Sette A, Mariuzza RA, J Mol Biol. 2002 May 31;319(2):449-61. PMID:12051920
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