[Research progress on the Co-Presentation of CD8⁺ T cell antigen epitopes by HLA-A*02 and HLA-E in infectious...

Human leukocyte antigen (HLA) plays a pivotal role in immune responses. As a classical HLA-Ia among the HLA molecules, HLA-A*02 activates CD8⁺ T cells by presenting endogenous antigenic peptides, thereby contributing significantly to antiviral immunity. In contrast, the non-classical HLA-Ib molecule HLA-E regulates immune homeostasis through interactions with the CD94/NKG2 receptor expressed on natural killer (NK) cells. Recent studies have revealed that HLA-E could also present pathogen or tumor-derived antigenic peptides to activate specific CD8⁺ T cells. Notably, the peptide sequences presented by HLA-E exhibit high similarity to those presented by HLA-A*02, suggesting potential cooperative or competitive mechanisms underlying their involvement in CD8⁺ T cell-mediated anti-pathogen immune responses. This review systematically compares the structural and functional bases of antigen presentation mechanisms, particularly focusing on their shared capacity to present pathogen-derived epitopes during infectious diseases for HLA-A*02 and HLA-E. We further discussed the roles of their co-presentation phenomenon in host defense and immune homeostasis maintenance. The design of novel peptide vaccines based on the co-presentation of antigenic epitopes by HLA-A*02 and HLA-E may overcome limitations posed by HLA polymorphism, offering a theoretical basis and novel strategies for achieving broader and longer-lasting immune protection.