Human leukocyte antigen class I molecules presenting poxvirus-derived peptides (HLA-I/Poxvirus pMHC)

Human leukocyte antigen (HLA) class I molecules presenting poxvirus-derived peptides are essential molecular complexes for the cellular immune recognition of orthopoxviruses, such as Variola (smallpox) and Mpox (PMID: 16148104). These complexes consist of a polymorphic HLA heavy chain, beta-2 microglobulin, and a specific viral peptide fragment derived from the proteasomal processing of poxvirus proteins within an infected cell. Their primary biological function is to display these intracellular antigens on the cell surface for surveillance by CD8+ cytotoxic T lymphocytes (PMID: 19535457). Upon binding to a cognate T-cell receptor, the complex initiates a signaling cascade that results in the targeted destruction of the infected host cell and the limitation of viral replication. In clinical practice, these peptide-MHC complexes are the functional targets of vaccines like JYNNEOS and ACAM2000, which prime the immune system to recognize these specific viral signatures. Furthermore, they are being investigated as targets for novel immunotherapies, including TCR-like monoclonal antibodies and adoptive T-cell transfers. However, poxviruses have evolved sophisticated mechanisms to inhibit peptide transport and downregulate HLA surface expression, posing a significant challenge for effective immune clearance (PMID: 11544341).

Other names

MHC class I-poxvirus peptide complexHLA-poxvirus epitope complexpMHC class I (poxvirus)Human leukocyte antigen-orthopoxvirus peptide complex

Presentation of intracellularly processed viral epitopes to CD8+ cytotoxic T lymphocytes (CTLs), which triggers T-cell receptor (TCR) recognition, secretion of pro-inflammatory cytokines (e.g., IFN-gamma), and direct lysis of the infected cell via perforin and granzymes.