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-1(H) 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-1(H) peptide (VLHDDLLEA) and HA-1(R) 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-1(H) peptide but not HA-1(R) 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-1(H) peptide but not HA-1(R) peptide; Group 2 - bind HA-1(R) peptide but not HA-1(H) peptide; Group 3 - bind both HA-1(H) and HA-1(R) 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.