Full-length DQ beta cDNA sequences of HLA-DR2/DQw1 subtypes: genetic interactions between two DQ beta loci generate human class II HLA diversity.
Two-dimensional gel electrophoresis of DQ molecules from three different Dw subtypes (Dw2, Dw12, and Dw21/FJO) of the HLA-DR2/DQw1 haplotype reveals that one alpha beta heterodimer of DQ molecule is expressed by each subtype and the DQ beta chain is electrophoretically variable among the three DR2/DQw1 subtypes. We have constructed cDNA libraries from the same homozygous typing cells used in the two-dimensional polyacrylamide gel electrophoresis analyses (HTC VYT for Dw2, HTC DHO for Dw12, and HTC FJO for Dw21/FJO) and isolated DQ beta cDNA clones with full-length coding sequences for each subtype. The deduced amino acid sequences show that the DQ beta chains of these three DR2/DQw1 subtypes are highly polymorphic and confirm their electrophoretic heterogeneity: for a mature protein of 229 amino acids, they differ with each other by 10-17 amino acids in the first domain and by 3-7 residues in the C-terminal sequence. Comparison among the available DQ beta sequences representing the four major DQ specificities (DQw1, DQw2, DQw3, and DQw4) in the DQ subregion as defined by serologic method suggests that (1) DR2,Dw2,DQw1 and DR3,DQw2 haplotypes probably interact with each other to generate the DQw3 and DQw4 beta alleles and (2) an evolutionary scheme may be proposed to relate the various beta alleles of the four major DQ specificities.
Wu
S K
SK
Department of Laboratory Medicine, University of Minnesota, Minneapolis.
Lu
D
D
Madden
M
M
Liu
C P
CP
Miyokawa
N
N
Bach
F H
FH
Saunders
T L
TL
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D002460:Cell Line; D003001:Cloning, Molecular; D015180:Electrophoresis, Gel, Two-Dimensional; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D015802:HLA-DR2 Antigen / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012689:Sequence Homology, Nucleic Acid
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C051568:HLA-DQ1 antigen; C057615:HLA-DQbeta antigen; D015802:HLA-DR2 Antigen