Novel insights into non-HLA alloimmunity in kidney transplantation

Transpl Int. 2020 Jan;33(1):5-17. doi: 10.1111/tri.13546. Epub 2019 Nov 28.


Recognition of non-self structures on donor cells represents the main immunological barrier in solid organ transplantation. The human leukocyte antigens (HLA) are considered the most important non-self (allo)antigens in transplantation. Long-term graft attrition is mainly caused by the formation of alloreactive antibodies that are directed against non-self structures (i.e., epitopes) on cell surface proteins. Recently published data provided evidence for a similar importance of non-HLA mismatches between donors and recipients in acute rejection as well as long-term kidney allograft survival. These data suggest a broader concept of immunological non-self that goes beyond HLA incompatibility and expands the current concept of polymorphic non-self epitopes on cell surface molecules from HLA to non-HLA targets. Amino acid substitutions caused by single nucleotide variants in protein-coding genes or complete loss of gene expression represent the basis for polymorphic residues in both HLA and non-HLA molecules. To better understand these novel insights in non-HLA alloimmunity, we will first review basic principles of the alloimmune response with a focus on the HLA epitope concept in donor-specific antibody formation before discussing key publications on non-HLA antibodies.

Keywords: donor-specific antibodies; epitopes; genome-wide incompatibility; non-HLA Alloimmunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epitopes
  • Graft Rejection / immunology*
  • Graft Survival*
  • HLA Antigens
  • Histocompatibility*
  • Humans
  • Kidney Transplantation*
  • Membrane Proteins / immunology


  • Epitopes
  • HLA Antigens
  • Membrane Proteins