Structural definition of the A*74 group: implications for matching in bone marrow transplantation with alternative donors.
We have identified two new A*74 alleles (A*7402 and 7403) in two unrelated individuals. A*7402 differs from A*7401 by a single amino acid substitution in the signal peptide and may be the result of a gene conversion event at the 3' end of exon 1. A*7403 differs from A*7401 by a single amino acid exchange in the alpha 1 domain and is most likely due to a point mutation in exon 2, since no HLA class I donor allele has been found. Since A*7402 appears to be the ancestor of the other two A*74 alleles, it is possible that A*7401 and 7403 have been created by successive point mutations. The sequences of the expressed proteins of A*7401 and 7402 are identical. The heavy chain sequence of A*7403 differs from these alleles at the crucial residue 79 which is located in the sequence stretch of the alpha 1 alpha-Helix where the Bw4/Bw6 determinants have been identified and which probably affects TCR interaction. This variation can therefore be expected to stimulate alloreactive T cells, graft rejection and graft versus host disease emphasizing the relevance for matching in bone marrow transplantation with alternative donors.
Department of Internal Medicine, Virchow-Klinikum, Humboldt-Universität Berlin, Germany. blasczyk@ukrv.de
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R
Blasczyk
J
J
Wehling
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Onaldi-Mohr
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V
Rebmann
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D
Chandanayingyong
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H
Grosse-Wilde
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003001:Cloning, Molecular / Q000379:methods; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data
D015234:HLA-A Antigens