The importance of HLA in companion diagnostics

The Major Histocompatibility Complex (MHC) genes encode for proteins used by the immune system to discriminate ‘self’ from ‘non-self’. In humans, the MHC is called Human Leukocyte Antigen (HLA). HLA proteins play a key role in our immune system by presenting peptides (antigens) to T cells. These peptides can originate from your own cells, from pathogens such as bacteria or viruses, or from donated stem cells and organs. The T cells only respond to HLA loaded with non-self peptides. In the context of transplantation, the HLA proteins of the donor need to fully match with the patient’s immune system in order to have a successful stem cell transplantation. If the HLA proteins are not matched, the transplanted immune cells will reject the cells of the patient since they are recognized as ‘non-self’.

Given the important role of HLA molecules in the immune system, over the past years they have become targets as potential biomarkers, especially in the field of oncology and immunotherapy, illustrated by several examples of HLA directed CAR T-cell therapies or HLA directed epitope vaccines against different cancer types. As these therapies require the screening of patients whom are most likely to benefit from the therapy, a clear need to develop HLA typing companion diagnostics.