HLA-DR4-associated haplotypes are genotypically diverse within HLA.
Biochemical diversity among products of class II HLA genes has been observed in individuals who appear to be HLA-D and DR-identical by cellular and serologic typing. We used techniques of restriction enzyme fragment analysis by Southern blotting to analyze this diversity at the level of cellular DNA. A panel of 17 HLA-DR4 homozygous cell lines (HCL) were investigated by using cDNA probes homologous to DQ beta, DQ alpha, and DR beta genes. Each probe was hybridized to cellular DNA digested with a series of different restriction endonucleases. Polymorphisms were observed with the use of the enzymes Pst I, Hind III, and Bam HI: Hybridization of cellular DNA digested with Hind III and Pst I with the DQ beta probe revealed specific polymorphisms, as did hybridization of the Pst I digest with the DQ alpha cDNA probe and the Bam HI digest with the DR beta probe. The observed differences fall into two categories: first, considerable diversity was seen between HLA-DR4 HCL that represent different HLA-D-defined haplotypes; second, diversity was also observed among HCL of the same DR4-associated HLA-D cluster. In contrast to the DQ cDNA probes, hybridization with the DR beta probe revealed relatively limited polymorphism by using a panel of different restriction endonucleases. Thus, although there is a general pattern of polymorphic restriction enzyme fragments homologous to DQ probes within an HLA-D cluster, the pattern seen for any particular cell line was not sufficiently distinct to assign an HLA-D or DR specificity.
Holbeck
S L
SL
Kim
S J
SJ
Silver
J
J
Hansen
J A
JA
Nepom
G T
GT
D002460:Cell Line; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D005802:Genes, MHC Class II; D005838:Genotype; D015804:HLA-DR4 Antigen; D006238:Haploidy; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D006824:Hybridization, Genetic; D011110:Polymorphism, Genetic
D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D004262:DNA Restriction Enzymes