Humanized transgenic mice expressing HLA DR4-DQ3 haplotype: Reconstitution of phenotype and HLA-restricted T-cell responses

Abstract

Many autoimmune conditions have close genetic linkages to particular human histocompatibility leukocyte antigen (HLA) class II genes. With the aim of establishing a murine model of autoimmune disease, we have generated an HLA DR4-DQ3 haplotype transgenic (Tg) mouse that expresses a 440-kb yeast artificial chromosome harbouring DRA, DRB1*040101, DRB4*010301, DQA1*030101, DQB1*0302 and all the internal regulatory segments. This Tg mouse line was crossed to human CD4 (hCD4) Tg mice and endogenous class II knockout mice (I-Ao/o and I-Eo/o) lines to generate a DR4-DQ3.hCD4.IAEo/o Tg line. The Tg DR and DQ molecules are expressed on the physiological cell types in these animals, i.e. on most B cel..