Significance of the HLA molecular structure to transplantation.
1. Residues in the first, second, and third domains of HLA-A,B,C, and the first domain of DR beta, DQ alpha, and DQ beta molecule have been assigned to unique A,B,C or DR specificities from the known amino acid sequences. Antibodies were noted to correlate with most of these variable amino acid residues. 2. We therefore conclude that most of the variable residues in the first domain function as immunogens against which the antibodies had been elicited. 3. If the variants at these positions are immunogens, then it follows that matching for transplantation should be done by considering mismatched amino acids rather than the private specificities, as performed today. 4. Molecular matching cannot be performed immediately for the HLA-A,B,C specificities since many specificities are not yet sequenced. For the DR and DQ specificities, the sequences are established, but antisera identifying the subtypes of DR and DQ are only now becoming available. Once patients are typed for the 23 DR beta alleles, 8 DQ alpha alleles and 13 DQ beta alleles, matching should be feasible. 5. Molecular matching combines both public and private specificity matching since it assumes that both types of antigens are distinct. A single extended DR mismatch may involve as many as 76 amino acid residues of mismatch. 6. True cross-reactivity of the HLA molecules can eventually be established through structural studies. Most of the previously described "cross-reactivities" are likely to be shared determinants.
Park
M S
MS
Terasaki
P I
PI
Barbetti
A
A
Han
H
H
Cecka
J M
JM
D000595:Amino Acid Sequence; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship; D014181:Transplantation Immunology
D000939:Epitopes; D006680:HLA Antigens; D007518:Isoantibodies