WHAT IS THE MAJOR HISTOCOMPATIBILITY COMPLEX AND ITS RELEVANCE TO ORGAN TRANSPLANTATION

The major histocompatibility complex (MHC) is a group of genes that encode proteins responsible for presenting antigens to the immune system. These proteins are crucial for the recognition of self and non-self cells, playing a key role in immune responses, particularly in distinguishing between healthy cells and pathogens or abnormal cells. The MHC is divided into two classes: class I MHC molecules are found on the surface of almost all nucleated cells and present antigens to cytotoxic T cells, while class II MHC molecules are primarily expressed on antigen-presenting cells such as macrophages, dendritic cells, and B cells, presenting antigens to helper T cells.

In organ transplantation, the compatibility of MHC molecules between the donor and recipient plays a critical role in determining the success of the transplant. Mismatched MHC molecules can trigger an immune response in which the recipient’s immune system recognizes the transplanted organ as foreign and attacks it, leading to rejection. Therefore, matching MHC antigens between donors and recipients is essential to minimize the risk of rejection and improve transplant outcomes.

In other words, the Major Histocompatibility Complex (MHC) is a family of genes that encode membrane proteins crucial for the immune response. In humans, MHC is known as Human Leukocyte Antigens (HLA). The MHC plays a vital role in antigen presentation, where peptides from cellular metabolism are captured and presented on cell surfaces for recognition by the immune system. MHC molecules are essential in distinguishing self from non-self antigens and play a significant role in immune responses.

The MHC, particularly HLA in humans, is of utmost importance in organ transplantation. When organs are transplanted from one individual to another, the recipient’s immune system recognizes the donor’s HLA molecules as foreign, triggering an alloimmune response. Matching donor and recipient for MHC antigens has been shown to improve graft acceptance significantly. However, mismatches in HLA alleles can lead to both cellular and antibody-mediated rejection of the transplanted organ.

In organ transplantation, especially with regards to antibody-mediated rejection (AMR), which is associated with poor outcomes, detecting donor-specific anti-HLA antibodies (DSA) is crucial. While serum DSA detection is commonly used for diagnosing AMR, there are challenges related to accuracy and sensitivity. Recent advancements have focused on detecting intra-graft DSA as an alternative method to overcome these limitations.