HLA

Human leukocyte antigen (HLA) refers to a set of genes in humans that encode cell-surface proteins responsible for presenting peptide antigens to T cells. The HLA region is located on the short arm of chromosome 6 (6p21) within the major histocompatibility complex (MHC). The proteins produced are essential for immune recognition and help distinguish self from non-self.

Two main classes of HLA molecules mediate antigen presentation: class I molecules (HLA-A, HLA-B, HLA-C) present endogenous peptides to CD8+ cytotoxic T cells, while class II molecules (HLA-DR, HLA-DQ, HLA-DP) present exogenous peptides to CD4+ helper T cells. The HLA genes are highly polymorphic, and each person expresses two different haplotypes co-dominantly, yielding a broad repertoire of peptide presentation. Polymorphism arises from many alleles; this diversity underpins tissue compatibility and immune responsiveness.

Clinical relevance: In transplantation, HLA compatibility between donor and recipient at multiple loci greatly influences graft survival and risk of rejection; typing typically includes HLA-A, -B, -C, -DRB1, and sometimes -DQ and -DP. HLA associations with diseases are well established: HLA-B27 with ankylosing spondylitis; HLA-DRB1 alleles with rheumatoid arthritis; HLA-DQ2/DQ8 with celiac disease. In pharmacogenomics, certain alleles predict drug hypersensitivity, such as HLA-B*57:01 and abacavir sensitivity, and HLA-B*15:02 with carbamazepine-induced Stevens–Johnson syndrome in specific populations.

Laboratory typing methods include serology and molecular techniques such as sequence-based typing and next-generation sequencing. The high degree of polymorphism and linkage disequilibrium within the MHC makes full HLA matching complex but essential for transplantation, autoimmunity research, and personalized medicine.