TY  - JOUR
AU  - Macdonald, WA
AU  - Purcell, AW
AU  - Misfud, NA
AU  - Ely, LK
AU  - Williams, DS
AU  - Chang, LN
AU  - Gorman, J
AU  - Clements, CS
AU  - Kjer-Nielsen, L
AU  - Koelle, DM
AU  - Burrows, SR
AU  - Tait, BD
AU  - Holdsworth, R
AU  - Brooks, AG
AU  - Lovrecz, GO
AU  - Lu, L
AU  - Rossjohn, J
AU  - McCluskey, J
Y2  - 2014/05/21
Y1  - 2003/09/01
SN  - 0022-1007
UR  - http://hdl.handle.net/11343/26196
AB  - 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.
N1  - application/pdf
LA  - English
PB  - ROCKEFELLER UNIV PRESS
KW  - Cellular Immunology; Immune System and Allergy
T1  - A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition
DO  - 10.1084/jem.20030066
IS  - Journal of Experimental Medicine
VL  - 198
IS  - 5
SP  - 679-691
L1  - /bitstream/handle/11343/26196/115962_5012.pdf?sequence=1&isAllowed=n
ER  -