HLAs

Human leukocyte antigens (HLAs) are cell-surface glycoproteins encoded by the human leukocyte antigen gene cluster within the major histocompatibility complex on chromosome 6. They present peptide fragments to T cells and are essential for immune recognition. HLAs are classified into three groups: class I (HLA-A, -B, -C) bind endogenous peptides and present them to CD8+ T cells; class II (HLA-DP, -DQ, -DR) bind exogenous peptides and present them to CD4+ T cells; class III contains other immune-related genes, including certain complement components and tumor necrosis factor.

HLAs are highly polymorphic and co-dominantly expressed, meaning individuals possess two alleles at each locus. This diversity expands the range of peptides that can be presented but complicates tissue matching for transplantation. Matching HLA alleles between donor and recipient reduces graft rejection and graft-versus-host disease risk. HLA typing uses serology and increasingly DNA-based methods, including sequencing and next-generation approaches.

Alleles have strong associations with disease risk and therapeutic response. For example, HLA-B27 is linked to ankylosing spondylitis, and HLA-DQ2/DQ8 alleles are associated with celiac disease; other HLA variants are implicated in type 1 diabetes and additional autoimmune conditions. Non-classical HLA molecules (HLA-E, HLA-F, HLA-G) show limited polymorphism and contribute to immune regulation and tolerance, including maternal-fetal interactions and NK cell recognition.

Nomenclature follows a structured system such as HLA-A*02:01, reflecting sequence variation. Population diversity in HLA alleles is high and shaped by evolutionary forces favoring balanced polymorphism. Together, HLAs coordinate adaptive immunity and influence outcomes in transplantation, autoimmunity, infectious disease, and cancer.