1N2R

A natural selected dimorphism in HLA B*44 alters self, peptide reportoire and T cell recognition.

Summary for 1N2R

• Entry DOI: 10.2210/pdb1n2r/pdb
• Related: 1M6O
• Descriptor: HLA class I histocompatibility antigen, BW-44(B-12) B*4403 alpha chain, Beta-2-microglobulin, HLA DPA*0201 PEPTIDE, ... (5 entities in total)
• Functional Keywords: mhc i, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30481; Secreted: P61769
• Total number of polymer chains: 3
• Total formula weight: 44936.76

Authors

Macdonald, W.A.,Purcell, A.W.,Williams, D.S.,Mifsud, N.,Ely, L.K.,Gorman, J.J.,Clements, C.S.,Kjer-Nielsen, L.,Koelle, D.M.,Brooks, A.G.,Lovrecz, G.O.,Lu, L.,Rossjohn, J.,McCluskey, J. (deposition date: 2002-10-24, release date: 2004-03-16, Last modification date: 2024-10-30)

Primary citation

Macdonald, W.A.,Purcell, A.W.,Mifsud, N.A.,Ely, L.K.,Williams, D.S.,Chang, L.,Gorman, J.J.,Clements, C.S.,Kjer-Nielsen, L.,Koelle, D.M.,Burrows, S.R.,Tait, B.D.,Holdsworth, R.,Brooks, A.G.,Lovrecz, G.O.,Lu, L.,Rossjohn, J.,McCluskey, J.
A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition.
J.Exp.Med., 198:679-691, 2003

PubMed Abstract: HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a high frequency in all human populations, and yet they only differ by one residue on the alpha2 helix (B*4402 Asp156-->B*4403 Leu156). CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphism at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B*4403 modifies both peptide repertoire and T cell recognition, and is reflected in the paradoxically powerful alloreactivity that occurs across this "minimal" mismatch. The findings suggest that these closely related class I genes are maintained in diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire.

PubMed: 12939341
DOI: 10.1084/jem.20030066

Experimental method

X-RAY DIFFRACTION (1.7 Å)