Human Leukocyte Antigen (HLA) Class I and II molecules (HLA-I/II)

Human Leukocyte Antigen (HLA) Class I and II molecules are highly polymorphic cell surface glycoproteins encoded by the Major Histocompatibility Complex (MHC) that play a central role in the adaptive immune system [1]. HLA Class I molecules (HLA-A, -B, -C) are expressed on all nucleated cells and present endogenous peptides to CD8+ cytotoxic T cells, while HLA Class II molecules (HLA-DR, -DQ, -DP) are primarily expressed on professional antigen-presenting cells and present exogenous peptides to CD4+ helper T cells [2]. These molecules are considered patient-specific due to their extreme genetic diversity, which determines an individual's ability to mount immune responses against specific pathogens or tumors [3]. In modern oncology, HLA molecules are critical targets for personalized medicine, particularly in the design of neoantigen vaccines and TCR-engineered T-cell therapies that must be matched to a patient's specific HLA genotype [4]. Loss of HLA expression or Loss of Heterozygosity (LOH) at the HLA locus is a well-documented mechanism of immune evasion in various cancers [5]. Beyond oncology, HLA molecules are the primary determinants of histocompatibility in organ and hematopoietic stem cell transplantation and are strongly associated with susceptibility to numerous autoimmune diseases [6].

Other names

Major Histocompatibility ComplexMHC Class I and IIHLA antigensHuman Leukocyte Antigens

HLA molecules act as the molecular scaffold for antigen presentation; they bind peptide fragments (derived from either intracellular proteins for Class I or extracellular proteins for Class II) and display them on the cell surface for recognition by T-cell receptors (TCRs), thereby initiating the adaptive immune response [1, 2].