STRUCTURAL DEFINITION OF THE A-ASTERISK-74 GROUP - IMPLICATIONS FOR MATCHING IN BONE-MARROW TRANSPLANTATION WITH ALTERNATIVE DONORS

We have identified two new A74 alleles (A*7402 and 7403) in two unrel ated individuals. A7402 differs from A*7401 by a single amino acid su bstitution in the signal peptide and may be the result of a gene conve rsion event at the 3' end of exon 1. A7403 differs from A*7401 by a s ingle 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 A7402 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 A7401 and 7402 are identical. The heavy chain sequence of A*7403 dif fers 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 dete rminants have been identified and which probably affects TCR interacti on, This variation can therefore be expected to stimulate alloreactive T cells, graft rejection and graft versus host disease emphasizing th e relevance for matching in bone marrow transplantation with alternati ve donors.