Human leukocyte antigen class I complex (HLA class I (HLA-I))

The Human leukocyte antigen class I complex is a cell-surface heterodimer composed of a polymorphic heavy (α) chain encoded by HLA-A, HLA-B, or HLA-C and an invariant β2-microglobulin light chain; it binds peptides—typically 8–10 amino acids—within a closed-ended groove formed by the α1/α2 domains and presents them to CD8+ T cells via TCR recognition, with the α3 domain engaging the CD8 co-receptor. HLA-I exhibits extreme polymorphism concentrated in the peptide-binding cleft, generating distinct binding pockets (A–F), where primary anchor interactions at pockets B (peptide position 2) and F (C-terminus) determine peptide specificity; these biochemical differences underlie HLA supertypes with overlapping motifs. HLA-I is expressed on virtually all nucleated cells and is central to antiviral and antitumor immunity, shaping adaptive responses and serving as a foundational component for T cell–mediated recognition, while its genetic diversity and expression have major implications for infection outcomes, cancer immunotherapy, autoimmunity, and transplantation.

Other names

HLA class IMajor histocompatibility complex class I (MHC class I) (human)HLA-A/HLA-B/HLA-C (class I heavy-chain loci)HLA-I heterodimer (heavy chain with β2-microglobulin)

Enhancement of T-cell mediated killing via restored/augmented presentation of tumor/viral peptides on HLA-I, enabling TCR recognition (checkpoint inhibitor mechanism dependency). Vaccine-induced CD8+ T-cell responses require peptide loading on HLA-I and subsequent TCR engagement. Peptide–HLA binding specificity determined by anchor residues engaging B and F pockets in the binding groove, dictating which epitopes are presented.