MHC class II alpha/beta heterodimeric cell surface molecules expressed from a single proviral genome

Transplantation tolerance to renal allografts can be induced in large anima l preclinical models if the donor and recipient have identical major histoc ompatibility complex (MHC) class II loci. Such class II matching is, howeve r, not clinically achievable owing to the extreme diversity of class II seq uences. With the ultimate goal of creating a somatic class II match in the bone marrow of an allograft recipient, the aim of the study is to develop a double-copy retrovirus construct to express both chains of the MHC class I I DQ glycoprotein on a single transduced cell. Analysis of the expression p atterns of the retroviral DQ transgenes in both virus producer and transduc ed fibroblasts revealed correct transcription and stable surface expression of the DQ heterodimers, In addition, we demonstrate that both the DQA and DQB sequences are functional within the same proviral copy, a prerequisite for efficient induction of transplantation tolerance following transduction of bone marrow precursor cells. The DQ double-copy retrovirus vector showe d efficient expression of the transferred class II cDNA in murine colony-fo rming units for the granulocyte-monocyte lineage (CFU-GM), indicating that it is suitable for gene therapy of multimeric proteins in hematopoietic cel ls.