A cellular and functional split in theDRw8haplotype is due to a single amino acid replacement (DRβser 57- asp 57)
✍ Scribed by Ann-Kristin Jonsson; Leif Andersson; Lars Rask
- Book ID
- 104736021
- Publisher
- Springer-Verlag
- Year
- 1989
- Tongue
- English
- Weight
- 885 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0093-7711
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✦ Synopsis
The single DR beta chain gene of the DRw8 haplotype has been suggested to carry both the DRw8 and the DRw52 epitopes. Cellular typing has shown that the DRw8 haplotype can be split into three subtypes, Dw8.1, Dw8.2, and Dw8.3, presumably due to a polymorphism in the DRw8~ chain. Furthermore, Dw8.1 and Dw8.2 cells present influenza virus antigen to different T-cell clones. In the present study, DRw8/Dw8.2/3 chain cDNA was cloned and characterized. A comparison of this sequence with a partial DRw8/Dw8.1 t3 chain gene suggested that the DRw8 split is due to a single amino acid replacement of set 57 -asp 57 caused by three nucleotide substitutions in the same codon. In most DR haplotypes, two expressed DR beta chain genes exist. Comparing the nucleotide sequence of the single beta gene in the DRw8 haplotype to those of other DR beta genes revealed that the DRw8 beta gene sequence is most closely related to the DRB1 genes of the DR3, 5, and w6 haplotypes. However, the comparisons also showed that it was not possible from sequence similarities to divide the DR beta genes into two or more distinct allelic series.
in the DRw8 haplotype to as many as four in the DR4 haplotype (B6hme et al. 1985). Two separate allelic series of DR specificities have been suggested on the basis of serological studies, the classical DRI-wl5 and the supertypic specificities DRw52/DRw53 (Albert et al. 1984). In addition to their DR specificities, haplotypes DR3, 5, w6, and w8 all express the DRw52 specificity, while haplotypes 4, 7, and 9 express the DRw53 specificity. Since there is a single DR beta gene in the DRw8 haplotype, it is reasonable to assume that the molecule encoded by this gene carries both the DRw8 and the DRw52 epitopes. The two expressed DR beta genes of DR haplotypes 3, 5, and w6 are expressed at highly different rates (Kratzin et al. 1986, Berdoz et al. 1987). Since the single DR beta gene of DRw8 apparently shares properties with both genes of the above haplotypes, a further characterization of the DRw8~ chain was undertaken. This investigation also suggested an explanation at the molecular level for the functional and cellular split noted for the DRw8 haplotype (Henin et al. 1985, Mickelson et al. 1983, Herrera et al. 1985).