Molecular modeling of the minor histocompatibility antigen HA-1 peptides binding to HLA-A alleles.
Mismatch of the minor histocompatibility antigen HA-1 has been shown to correlate with graft-versus-host disease in HLA-matched sibling marrow transplants. The HA-1H peptide (VLHDDLLEA) that generates this response is known to be presented by HLA-A*0201. In order to understand the interaction of HA-1 peptides with other HLA-A alleles, we have used the LOOK interface to construct molecular models of both HA-1H peptide (VLHDDLLEA) and HA-1R peptide (VLRDDLLEA) binding with 103 HLA-A alleles. The results show that in addition to A*0201, 21/103 other HLA-A alleles should be able to bind HA-1H peptide but not HA-1R peptide. Based on the modeled predictions, HLA alleles can be categorised into 4 groups with respect to their interaction with HA-1 peptides: Group 1 - bind HA-1H peptide but not HA-1R peptide; Group 2 - bind HA-1R peptide but not HA-1H peptide; Group 3 - bind both HA-1H and HA-1R peptides; Group 4 - bind neither peptide. These predicted binding patterns of HA-1 peptides will be useful as an aid for defining a wider pool of HLA-A alleles in which HA-1 disparities among donor-recipient pairs can be investigated.
Ren
E C
EC
Department of Microbiology, WHO Collaborating Center for Immunology, National University of Singapore, Singapore. micrenec@nus.edu.sg
Kangueane
P
P
Kolatkar
P
P
Lin
M T
MT
Tseng
L H
LH
Hansen
J A
JA
D000483:Alleles; D015234:HLA-A Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*
C110615:HA-1 antigen; D015234:HLA-A Antigens; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides