Minor Histocompatibility Antigens: Molecular targets for immunomodulation in tissue transplantation and tumor therapy

Abstract

Even after matching the alleles for the major histocompatibility complexes (MHC), grafts are rejected in a considerable percentage of transplant recipients by the host immune system. In these patients, the host T cells recognize unique antigenic peptides on the cells from the transplanted grafts. These peptides are different from that of hosts due to non-MHC polymorphic differences between the host and the donor. To distinguish between the MHC and these, they were termed minor histocompatibility (mH) complexes. Thus, mH antigens (mH-Ags) are historically defined as allo-peptides derived from allelic gene products that are capable of eliciting T cell responses. Because of their significance in determining the clinical outcome of graft acceptance and graft-versus-host disease (GvHD), mH-Ags have been intensively studied for decades. Also, a strong T cell mediated immune response to mH antigenic peptides has the potential for formulating adoptive cellular immunotherapy for patients with hematological malignancies (Graft-versus-Leukemia, GvL). Utilizing recent technological advances the identities of many human and murine mH antigenic peptides have been defined towards achieving clinical applications. These antigenic peptides are currently being evaluated in clinical or basic immunological studies for their ability to produce effective T cell responses. Furthermore, to our surprise recent studies have revealed that some of the full-length mH proteins-themselves may possess specialized immune functions. This novel discovery is dictating a paradigm shift to redefine the functionality of mH-Ags. Given that the novel immune regulatory functions of mH-Ags can also be harnessed; the possibilities to formulate additional cancer immunotherapies are expanding.