Human leukocyte antigen complex (HLA complex) (HLA)

The Human Leukocyte Antigen (HLA) complex, the human version of the Major Histocompatibility Complex (MHC), is a highly polymorphic system of genes located on chromosome 6 that encodes cell surface glycoproteins essential for immune recognition. These molecules function by presenting peptide antigens to T-cell receptors (TCRs); HLA Class I molecules (HLA-A, -B, -C) present endogenous peptides to CD8+ cytotoxic T cells, while HLA Class II molecules (HLA-DR, -DQ, -DP) present exogenous peptides to CD4+ helper T cells (Rock et al., 2016, Nat Immunol). In the context of hematopoietic and leukemic cells, HLA molecules are the primary determinants of histocompatibility in allogeneic stem cell transplantation and are the targets of the Graft-versus-Leukemia (GVL) effect. However, leukemic cells often evade immune surveillance through "HLA loss," where genomic alterations like Loss of Heterozygosity (LOH) at the HLA loci result in the disappearance of the mismatched HLA alleles recognized by donor T cells, leading to disease relapse (Vago et al., 2009, N Engl J Med). Therapeutic interventions include the use of immunosuppressants to manage HLA-mediated graft-versus-host disease and the development of HLA-restricted TCR-engineered T cells and bispecific antibodies designed to target specific HLA-peptide complexes on malignant cells (Mehta et al., 2021, Blood).

Other names

Major Histocompatibility ComplexMHCHLA lociHuman MHCHLA class I and II

HLA molecules present peptide antigens to T-cell receptors (TCRs) to initiate and regulate adaptive immune responses (Rock et al., 2016, Nat Immunol).