A chimeric MHC class II complex was created by fusing the human peptide binding domains of class II alpha and beta chains to the CD4 binding domains of murine class II alpha or beta chains. The was done by the construction of two separate transgene constructs. The alpha1 and beta1 domains isolated from human DRA1*0101 and DRB1*0101 replaced the corresponding alpha1 and beta1 domains of the H2-Ea and H2-Eb1 genes that make up mouse I-Ed. The native murine promoters were left intact. These transgene constructs were co-injected into fertilized oocytes and the founder mice with the highest expression of the chimeric MHC was chosen for further propagation. Flow cytometry analysis indicates that virtually all cells in peripheral blood that express endogenous MHC-II also express the chimeric MHC-II. The transgene construct was later shown (in J:126700) to have inserted into chromosome 5.