Cytomegalovirus peptide-MHC class I complex (CMV pMHC-I)

Cytomegalovirus (CMV) peptide antigens presented by MHC class I molecules are critical targets for the immune system to identify and eliminate CMV-infected cells [MDPI, https://doi.org/10.3390/ijms252312845; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590112/]. These complexes consist of viral peptides, primarily derived from immunodominant proteins like pp65 (UL83) and IE1 (UL123), which are processed by the proteasome and loaded onto Major Histocompatibility Complex (MHC) class I molecules (Human Leukocyte Antigen or HLA in humans) for presentation on the cell surface [MDPI, https://doi.org/10.3390/ijms252312845; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590112/]. Recognition of these pMHC complexes by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs) triggers the release of perforins and granzymes, leading to the lysis of the infected cell [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006732/; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590112/]. In clinical settings, these complexes are targeted by adoptive T-cell therapies, TCR-engineered T cells (TCR-T), and TCR-like antibodies to treat refractory CMV infections in transplant recipients or to target CMV-expressing tumors like glioblastoma [ASH Publications, https://doi.org/10.1182/blood-2021-153279; MDPI, https://doi.org/10.3390/ijms252312845]. However, CMV has evolved sophisticated immune evasion mechanisms, such as the US2-US11 proteins, which downregulate MHC class I expression to avoid detection [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006732/; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590112/]. Therapeutic strategies aim to bypass these evasion tactics or restore the host's antiviral T-cell immunity using partially HLA-matched or autologous cell products [ASH Publications, https://doi.org/10.1182/blood-2020-136337; TMC.edu, https://www.tmc.edu/news/2023/01/posoleucel-phase-ii/].

Other names

CMV peptide-HLA complexCMV pMHCCMV-specific MHC class Ipp65-HLA-A*02:01 complexIE1-HLA complexCytomegalovirus antigen-MHC class I complex

Recognition by T-cell receptors (TCRs) on CD8+ T cells, leading to T-cell activation, cytokine release (IFN-gamma, TNF-alpha), and granzyme/perforin-mediated lysis of the target cell [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006732/; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590112/].