PDBsum entry 3ft3

Immune system

PDB id: 3ft3

Contents

Protein chains

275 a.a. *

100 a.a. *

Ligands

VAL-LEU-HIS-ASP-ASP-LEU-LEU-GLU-ALA

Waters ×155

* Residue conservation analysis

PDB id:

3ft3

Name:

Immune system

Title:

Crystal structure of the minor histocompatibility peptide ha-1his in complex with hla-a2

Structure:

Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a. Synonym: mhc class i antigen a 2. Engineered: yes. Mutation: yes. Beta-2-microglobulin. Chain: b. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla, hla-a, hlaa. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m, beta-2 microglubuline, cdabp0092, hdcma22p. Synthetic: yes. Other_details: synthesized peptide

Resolution:

1.95Å R-factor: 0.184 R-free: 0.231

Authors:

J.-B.Reiser,S.Gras,A.Chouquet,M.Le Gorrec,E.Spierings,E.Goulmy, D.Housset

Key ref:

E.Spierings et al. (2009). Steric hindrance and fast dissociation explain the lack of immunogenicity of the minor histocompatibility HA-1Arg Null allele. J Immunol, 182, 4809-4816. PubMed id: 19342659

Date:

12-Jan-09 Release date: 28-Apr-09

Protein chain

P04439  (1A03_HUMAN) -  HLA class I histocompatibility antigen, A alpha chain from Homo sapiens

Seq: 365 a.a.

Struc: 275 a.a.*

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 100 a.a.*

* PDB and UniProt seqs differ at 21 residue positions (black crosses)

J Immunol 182:4809-4816 (2009)

PubMed id: 19342659

Steric hindrance and fast dissociation explain the lack of immunogenicity of the minor histocompatibility HA-1Arg Null allele.

E.Spierings, S.Gras, J.B.Reiser, B.Mommaas, M.Almekinders, M.G.Kester, A.Chouquet, M.Le Gorrec, J.W.Drijfhout, F.Ossendorp, D.Housset, E.Goulmy.

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.