Molecular analysis of the serologically defined HLA-Aw19 antigens. A genetically distinct family of HLA-A antigens comprising A29, A31, A32, and Aw33, but probably not A30.
The HLA-Aw19 complex consists of a number of serologically cross-reactive Ag (i.e., A29, A30, A31, A32, and Aw33) which exhibit an epitope shared by HLA-B and -C proteins. To investigate the structural basis for these serologic cross-reactivities, we have cloned and determined the nucleotide sequences for A30, A31, and Aw33, and compared the predicted amino acid sequences with those already available for A29, A32, and other class I allelic products. All alleles of the Aw19 group contained A-locus-specific sequences, exhibiting "A-ness." The structural similarities between Aw19 polypeptides were found in the alpha 1 and alpha 2 domains, where shared amino acid residues were identified that correlated with observed serological reactivity patterns. Seven Aw19-specific nucleotides were found. Two of these were silent substitutions, but the remaining five resulted in Aw19-specific amino acid residues. Each of the HLA-A alleles can be classified into one of the five serologically cross-reacting groups. In the Aw19 group, the alleles A29, A31, A32, and Aw33 are closely related serologically as well as genetically whereas A30 probably belongs to the A1/A3/A11 group. The similarity between A30 and the other Aw19 alleles may have resulted from two independent gene conversions affecting exons 2 and 3. Additional mutations or gene conversion-like events in A30 were also noted. It is postulated that gene conversions have played a significant role in the divergence of the Aw19 alleles. However, each serologically cross-reactive Aw19 allotype appears to have arisen directly from a common ancestral allele. A30 was the only exception, and this allele may represent an unusual allotype, which is subject to a high rate of genetic changes, as is seen in the H-2Kb gene of the mouse.
Kato
K
K
Laboratory of Human Immunogenetics, Memorial Sloan-Kettering Cancer Center, New York 10021.
Trapani
J A
JA
Allopenna
J
J
Dupont
B
B
Yang
S Y
SY
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics / Q000302:isolation & purification; D005785:Gene Conversion; D005805:Genes, MHC Class I; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family
D000939:Epitopes; D015234:HLA-A Antigens; C043205:HLA-A19 antigen; D015235:HLA-B Antigens; D015236:HLA-C Antigens