Serologic cross-reactivities poorly reflect allelic relationships in the HLA-B12 and HLA-B21 groups. Dominant epitopes of the alpha 2 helix.
Previous analysis has emphasized the correlation between primary structures of class I HLA molecules and their patterns of serologic cross-reactivity. Here we describe the structures of two serologic groups of HLA-B alleles for which this is not the case. HLA-B45, an allele associated with black populations, is serologically paired with B44 in the B12 group; its structure, however, is divergent from that of B44 but closely related to B50. The BN21 (B*4005) allele is associated with native Americans and is serologically grouped with B50 in the B21 group; its structure, however, is more closely related to alleles of the B40 group. The B44 and B45 serologically cross-reactive molecules differ at seven functional positions of the Ag recognition site; the B50 and BN21 molecules differ at four such residues. These differences are predicted to alter peptide presentation and be capable of eliciting strong alloreactive T cell responses. For these pairs of B12 and B21 Ag, serology appears dominated by epitopes formed by short sequences of the alpha 2 helix which have been shuffled by recombination between alleles. The implications of these results for HLA matching in transplantation are discussed.
Hildebrand
W H
WH
Department of Cell Biology, Stanford University, CA 94305.
Madrigal
J A
JA
Belich
M P
MP
Zemmour
J
J
Ward
F E
FE
Williams
R C
RC
Parham
P
P
D000483:Alleles; D000595:Amino Acid Sequence; D003429:Cross Reactions; D000939:Epitopes; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D044469:Racial Groups; D016415:Sequence Alignment
D000939:Epitopes; D015235:HLA-B Antigens; C035015:HLA-B12 antigen; C063569:HLA-B21 antigen