1EEZ

Crystal Structure Determination of HLA-A2.1 Complexed to GP2 Peptide Variant(I2L/V5L)

Summary for 1EEZ

• Entry DOI: 10.2210/pdb1eez/pdb
• Related: 1EEY 1QR1
• Descriptor: HLA-A2.1 MHC CLASS I (HEAVY CHAIN), BETA-2-MICROGLOBULIN (LIGHT CHAIN), GP2 PEPTIDE, ... (4 entities in total)
• Functional Keywords: major histocompatibility complex, peptide binding, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P01884
• Total number of polymer chains: 6
• Total formula weight: 89263.40

Authors

Sharma, A.K.,Kuhns, J.J.,Collins, E.J. (deposition date: 2000-02-04, release date: 2003-06-10, Last modification date: 2024-10-30)

Primary citation

Sharma, A.K.,Kuhns, J.J.,Yan, S.,Friedline, R.H.,Long, B.,Tisch, R.,Collins, E.J.
Class I major histocompatibility complex anchor substitutions alter the conformation of T cell receptor contacts.
J.Biol.Chem., 276:21443-21449, 2001

PubMed Abstract: An immunogenic peptide (GP2) derived from HER-2/neu binds to HLA-A2.1 very poorly. Some altered-peptide ligands (APL) of GP2 have increased binding affinity and generate improved cytotoxic T lymphocyte recognition of GP2-presenting tumor cells, but most do not. Increases in binding affinity of single-substitution APL are not additive in double-substitution APL. A common first assumption about peptide binding to class I major histocompatibility complex is that each residue binds independently. In addition, immunologists interested in immunotherapy frequently assume that anchor substitutions do not affect T cell receptor contact residues. However, the crystal structures of two GP2 APL show that the central residues change position depending on the identity of the anchor residue(s). Thus, it is clear that subtle changes in the identity of anchor residues may have significant effects on the positions of the T cell receptor contact residues.

PubMed: 11287414
DOI: 10.1074/jbc.M010791200

Experimental method

X-RAY DIFFRACTION (2.3 Å)