3FT4

Crystal Structure of the minor histocompatibility peptide HA-1Arg in complex with HLA-A2

Summary for 3FT4

• Entry DOI: 10.2210/pdb3ft4/pdb
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, arginine variant HA-1 peptide, ... (4 entities in total)
• Functional Keywords: hla, human minor h antigens, antigen processing, antigen presentation, immune response, immunogenicity, membrane, mhc i, polymorphism, transmembrane, immunoglobulin domain, graft rejection, host-versus-graft disease, graft-versus-tumor immune system, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769
• Total number of polymer chains: 3
• Total formula weight: 44805.79

Authors

Reiser, J.-B.,Gras, S.,Chouquet, A.,Le Gorrec, M.,Spierings, E.,Goulmy, E.,Housset, D. (deposition date: 2009-01-12, release date: 2009-04-28, Last modification date: 2024-10-16)

Primary citation

Spierings, E.,Gras, S.,Reiser, J.B.,Mommaas, B.,Almekinders, M.,Kester, M.G.,Chouquet, A.,Le Gorrec, M.,Drijfhout, J.W.,Ossendorp, F.,Housset, D.,Goulmy, E.
Steric hindrance and fast dissociation explain the lack of immunogenicity of the minor histocompatibility HA-1Arg Null allele.
J.Immunol., 182:4809-4816, 2009

PubMed Abstract: The di-allelic HLA-A2 restricted minor histocompatibility Ag HA-1 locus codes for the highly immunogenic HA-1(His) and the nonimmunogenic HA-1(Arg) nonapeptides, differing in one amino acid. The HA-1(His) peptide is currently used for boosting the graft-vs-tumor responses after HLA matched HA-1 mismatched stem cell transplantation; usage of the HA-1(Arg) peptide would significantly enlarge the applicability for this therapy. Our studies on mechanisms causing the HA-1 unidirectional immunogenicity revealed marginal differences in proteasomal digestion, TAP translocation, and binding affinity, whereas both dissociation rates and structural analyses clearly showed marked differences in the stability of these two HLA-A2 bound alleles. These data provide a rationale for the lack of HA-1(Arg) peptide immunogenicity essential for the choice of tumor peptides for stem cell-based immunotherapeutic application.

PubMed: 19342659
DOI: 10.4049/jimmunol.0803911

Experimental method

X-RAY DIFFRACTION (1.9 Å)