HLA-A Protein, Human (His)

HLA-C*0304, an antigen-presenting major histocompatibility complex class I (MHCI) molecule, plays a crucial role in both reproduction and antiviral immunity. In collaboration with B2M/beta 2 microglobulin, it exhibits a limited repertoire of self and viral peptides, serving as a prominent ligand for both inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on natural killer (NK) cells. Particularly in the context of pregnancy, HLA-C*0304 mediates the interaction between extravillous trophoblasts and uterine NK cells through KIR, thereby regulating trophoblast invasion essential for placentation and overall fetal growth. During viral infections, it presents viral peptides with low affinity for KIRs, preventing KIR-mediated inhibition and promoting the lysis of infected cells. Furthermore, HLA-C*0304 displays a restricted repertoire of viral peptides on antigen-presenting cells, facilitating recognition by alpha-beta T cell receptors on CD8-positive T cells, thereby guiding antigen-specific T cell immune responses to eliminate infected cells, especially in chronic viral infection scenarios such as HIV-1 or CMV infection. The peptide and the MHC molecule jointly contribute to antigen recognition, with the peptide determining fine specificity, and MHC residues dictating T cell receptor restriction. Typically presenting intracellular peptide antigens of 9 amino acids originating from cytosolic proteolysis via the proteasome, HLA-C*0304 exhibits binding preferences for peptides with specific anchor residues at positions 2 and 9, mainly comprising hydrophobic or aromatic amino acids (Phe, Ile, Leu, Met, Val, and Tyr).