Hierarchy in the assembly of HLA-B27 and HLA-Cw3 molecules in transgenic mice

Cell surface expression of human class I molecules in transgenic mice is dependent upon the available pool of ₂-microglobulin (₂m) and the affinity between mouse ₂m and human class I molecules. HLA-B27 and HLA-Cw3 transgenes can be expressed in mouse strains of the H-2 haplotypes b,f,k, and s which encode two endogenous class I genes mapping to H-2K and H-2D. The human class I genes cannot be expressed on H-2 ^dand H-2 ^qhaplotypes which encode three endogenous class I molecules (K,D,L). This suggests that there may be only enough mouse ₂m molecules to support three class I molecules. When both the HLA-B27 and HLA-Cw3 genes are introduced into H-2 ^bmice, only HLA-Cw3 reaches the cell surface. This suggests that HLA-Cw3 has a higher affinity than HLA-B27 for mouse ₂m. The possible implications of our findings regarding the assembly, transport, and expression of class I MHC molecules in vivo are discussed.