Class I antigens – HLA-A, -B, and -C.

HLA-A, -B, and -C are expressed on all cells. They are involved in antigen presentation to cytotoxic CD8+ T cells, while HLA-C is implicated in natural killer (NK) antigen recognition. In the past, HLA-A and -B were the only class I antigens routinely typed for transplantation, but it has recently been demonstrated that disparity at the HLA-C locus may be associated with higher rates of graft rejection and graft-versus-host disease (GVHD) following unrelated stem cell transplantation.

Serologic methods are still used to type class I antigens, but more precise molecular methods are available and have led to more precise HLA typing than was previously available through serologic typing alone. In related transplants, serology is often adequate. The one exception is homozygosity of one of the antigens. In this case, there may be allele-level differences that need to be sorted out with molecular typing. In unrelated transplants, allele-level typing is preferable.

Through the use of allele-level typing, disease-free survival for matched unrelated hematopoietic stem cell transplantation (HSCT) is beginning to approach that for HSCT from HLA-identical siblings. However, rates of GVHD and nonrelapse mortality are still higher for recipients of unrelated marrow.

Class II antigens – HLA-DR, DQ, and DP.

Class II antigens are recognized by CD4+ T cells. They are principally expressed on B cells, macrophages, and dendritic cells, and in some other cells to a more limited degree.

It is clear that serologic typing is inadequate for class II typing, and molecular typing is employed routinely.

HLA-DQ and DP are less important in allogeneic HSCT than HLA-DR, although some studies suggest a role for both in the pathogenesis of GVHD.