HLA-A*02:01–CMV pp65 NLVPMVATV peptide complex (HLA-A2/NLV)

The HLA-A*02:01–CMV pp65 NLVPMVATV peptide complex is a specific peptide-major histocompatibility complex (pMHC) class I molecule that plays a critical role in the cellular immune response against Human Cytomegalovirus (CMV) (Source: UniProt P01892). It consists of the HLA-A*02:01 heavy chain, β2-microglobulin, and the immunodominant 9-mer peptide NLVPMVATV (residues 495–503) derived from the CMV tegument protein pp65 (Source: PubMed 8623490). This complex is expressed on the surface of CMV-infected cells and is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (Source: PubMed 15123755). In clinical medicine, this complex is a primary target for monitoring CMV-specific immune reconstitution in hematopoietic stem cell and solid organ transplant recipients (Source: PubMed 10359566). Furthermore, it serves as a target for adoptive T-cell therapies and TCR-engineered T cells designed to treat refractory CMV infections (Source: ClinicalTrials.gov NCT04354311). Therapeutic strategies often involve the infusion of donor-derived or off-the-shelf T cells that specifically bind this pMHC to eliminate infected cells. Understanding the structural biology of this complex is essential for developing high-affinity TCR-based drugs and vaccines while minimizing the risk of cross-reactivity with human self-peptides.

Other names

HLA-A*02:01/pp65(495-503)A2-NLVPMVATVCMV pp65-A2 complexHLA-A*02:01-UL83(495-503)HLA-A2-NLV

The complex serves as a specific ligand for T-cell receptors (TCRs); therapeutic agents such as TCR-T cells or bispecific molecules bind to this pMHC complex to trigger the directed lysis of CMV-infected cells by cytotoxic T lymphocytes.