Expression of HLA-B27 in transgenic mice is controlled by gene(s) mapping between H-2D and H-2L loci.
The level of HLA-B27 transgene expression on the cell surface is dependent on the host H-2 haplotype. Mice homozygous for the H-2b, H-2f, H-2s, H-2p, H-2r, and H-2k haplotypes express B27 at high levels. An intermediate level of B27 expression is observed in H-2v mice whereas low levels of B27 are expressed in H-2q and H-2d mice. The decreased expression of B27 maps to the D region of the major histocompatibility complex. Recombinant strain B10.RKDB (DdLb) mapped the low expression gene centromeric to H-2L. In order to determine the low expression within the H-2D region, the B27 transgene was introduced into B10.D2-H-2dm1 and BALB/c-H-2dm2 mice. Expression of B27 in both of these strains was high indicating that neither H-2Dd nor H-2Ld is responsible for the low expression. This maps the effect between the H-2D and H-2L loci. In addition, introduction of human beta 2-microglobulin (beta 2m) into B10.D2-B27 transgenic mice caused a marked enhancement of B27 expression on the cell surface suggesting that the defect in B27 expression in certain haplotypes is due to an inability of B27 to associate with endogenous mouse beta 2m. We propose that gene(s) mapping between D and L (either D2, D3, D4, or some as yet unidentified gene) may be involved in class I assembly by helping association of beta 2m with class I. This putative molecule, designated "Assembly Enhancer (AE)" might have a negative influence in the association between human class I and mouse beta 2m.
Nickerson-Nutter
C L
CL
Department of Immunology, Mayo Clinic, Rochester, MN 55905.
Hogen
K L
KL
David
C S
CS
D000818:Animals; D002874:Chromosome Mapping; D006183:H-2 Antigens / Q000235:genetics*; D015796:HLA-B27 Antigen / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D051379:Mice; D008822:Mice, Transgenic; D001613:beta 2-Microglobulin / Q000378:metabolism
D006183:H-2 Antigens; D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin