HLA matching

HLA matching

Allograft rejection is directed against human leukocyte anti gens (HLAs). These are a group of cell surface glycoprotein molecules. HLA molecules are divided into class I (A, B and C) and class II (DR, DP and DQ). Class I molecules are expressed e xpressed by antigen-presenting cells (APCs) such as dendritic cells and B lymphocytes. HLA molecules are encoded for in the major histocompatibility complex (MHC) on chromosome 6. They are highly polymorphic, i.e. their amino acid sequences di ff er widely between individuals . To give an example, there are >1000 variants of the HLA-B gene. This genetic vari - ability means that most transplant donors and recipients have di ff erent HLA profiles. Donors and transplant recipients are HLA-typed using DNA sequencing. The antigens at HLA-A, -B and -DR are together described as the tissue type. The lev el of mismatch between the HLA molecules deter - mines the strength of the immune response. Every individual has two copies of each HLA gene and so for each locus (A, B or DR) it is possible to have 0, 1 or 2 mismatched genes. As the number of mismatches increases so does the chance of immune recognition and r ejection. The best matched grafts are described as having a mismatch of 0–0–0, i.e. no mis - matches at A, B or DR, respectively . A completely mismatched graft would be annotated as a 2–2–2 mismatch. The e ff ects of the di ff erent HLA antigens are not uniform. DR mismatches have a more powerful e ff ect than B mismatches , and A mis - matches are the least important. The tissue types of potential renal transplant recipients are held by national organisations, - such as NHS Blood and Transplant in the UK, and used to allocate donor organs to patients with the lowest level of HLA mismatch.