histocompatibility

Histocompatibility refers to the compatibility of tissues between donor and recipient with respect to immune recognition.

In humans, the major determinant is the human leukocyte antigen (HLA) system, part of the major histocompatibility complex (MHC). HLA genes are highly polymorphic and encode cell-surface glycoproteins that present peptide fragments to T cells. Class I molecules (HLA-A, -B, -C) present to CD8+ T cells; class II molecules (HLA-DR, -DQ, -DP) present to CD4+ T cells. The HLA genes are located on chromosome 6 in the human MHC region.

Matching HLA alleles between donor and recipient improves transplant outcomes. In solid organ transplantation, better HLA matching at key loci (A, B, DR) is associated with longer graft survival; immunosuppression is required to prevent rejection. In hematopoietic stem cell transplantation, high-resolution matching at HLA-A, -B, -C, -DRB1 (and often -DQB1) substantially reduces graft-versus-host disease and improves engraftment.

Rejection is driven by T cell recognition of non-self HLA antigens, and can be augmented by antibodies. Even with matched HLA, minor histocompatibility antigens—polymorphic peptides derived from other proteins—can provoke immune responses. Antibody-mediated incompatibilities are detected by crossmatching.

Histocompatibility testing employs HLA typing (serology and DNA-based methods) and functional assays such as mixed lymphocyte culture. The concept extends to transfusion medicine and reproductive biology, where antigen compatibility influences outcomes.