HLA class I histocompatibility antigen, C alpha chain (HLA-C*03:03) (HLA-C*03:03)

HLA-C*03:03 is a specific allele of the Human Leukocyte Antigen C (HLA-C) gene, which encodes a Major Histocompatibility Complex (MHC) class I heavy chain. This molecule plays a critical role in the adaptive immune system by presenting endogenous peptides, including viral and tumor-derived antigens, to CD8+ T cells. It also serves as a ligand for inhibitory and activating killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells, thereby regulating innate immune surveillance (Source: UniProt P10321; NIH Gene ID 3107). In oncology, HLA-C*03:03 has gained significant attention as a restriction element for T-cell receptor (TCR) therapies targeting common driver mutations, such as KRAS G12D, in patients with colorectal and pancreatic cancers (Source: PubMed 27923404). Therapeutic strategies involving this target primarily focus on TCR-engineered T cells designed to recognize specific peptide-HLA complexes, making patient HLA typing a prerequisite for treatment. Challenges in targeting this molecule include potential immune escape through HLA loss of heterozygosity and the need to ensure TCR specificity to avoid cross-reactivity with other HLA alleles.

Other names

MHC class I antigen C*03:03HLA-Cw*0303Human leukocyte antigen C*03:03Major histocompatibility complex, class I, C (HLA-C)

Presents intracellular peptide fragments (antigens) to CD8+ cytotoxic T cells and interacts with killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells to modulate immune activity.