Histocompatibility antigens play a crucial role in transplantation. These unique cell surface proteins trigger immune responses against foreign tissue, leading to graft rejection. Understanding their function is key to successful organ transplants.

Major Histocompatibility Complex (MHC) genes are central to transplantation. Their high variability between individuals makes finding compatible donors challenging. Matching MHC types between donor and recipient significantly improves graft survival rates.

Histocompatibility and Graft Rejection

Role of histocompatibility antigens

• Histocompatibility antigens act as unique cell surface proteins varying between individuals
• Function in graft rejection by triggering recipient's immune response against transplanted tissue
• Types include major histocompatibility complex (MHC) and minor histocompatibility antigens
• Recognition mechanisms involve T cell receptors binding to MHC-peptide complexes activating T cells leading to graft rejection

MHC in transplantation

• MHC genes located on chromosome 6 in humans exhibit high polymorphism
• MHC classes: Class I expressed on all nucleated cells, Class II on antigen-presenting cells
• Human Leukocyte Antigens (HLA) represent human version of MHC
• Mismatch between donor and recipient MHC increases rejection risk while matching improves graft survival
• MHC molecules present peptides to T cells essential for immune recognition and response

Types of graft rejection

• Hyperacute rejection occurs within minutes to hours post-transplantation mediated by preformed antibodies against donor antigens resulting in rapid graft failure
• Acute rejection develops days to weeks after transplantation involving T cell-mediated response against donor antigens characterized by inflammation and tissue damage
• Chronic rejection occurs months to years post-transplantation involving both cellular and humoral immune responses leading to progressive fibrosis and loss of graft function
• Cellular mechanisms:
  1. Cytotoxic T lymphocytes directly kill donor cells
  2. Helper T cells activate other immune cells
• Humoral mechanisms involve antibodies produced against donor antigens and complement activation leading to tissue damage

HLA typing for compatibility

• HLA typing methods include serological testing and DNA-based techniques (PCR, sequencing)
• Matching criteria focus on six major HLA antigens: HLA-A, B, and DR (two of each) with higher degree of matching correlating with better outcomes
• Applications include solid organ transplantation and hematopoietic stem cell transplantation
• Cross-matching detects preformed antibodies against donor HLA preventing hyperacute rejection
• Importance varies by transplant type with kidney transplants requiring crucial HLA matching for long-term graft survival while heart and lung transplants emphasize less on HLA matching due to time constraints
• Unrelated donor registries facilitate finding matched donors for patients without related donors
• Emerging technologies like next-generation sequencing enable high-resolution HLA typing and epitope matching for improved compatibility assessment