Human telomerase reverse transcriptase peptide–major histocompatibility complex class I complex (hTERT peptide–MHC complex)

The hTERT peptide–MHC complex is a cell-surface protein complex formed when peptides derived from human telomerase reverse transcriptase (hTERT), a protein highly expressed in the majority of human cancers but not in most normal somatic tissues, are processed and loaded onto major histocompatibility complex (MHC) class I molecules within a cell. These complexes are then exported to the cell surface, where they are recognized by the T cell receptor (TCR) on cytotoxic T lymphocytes, providing a mechanism for immune surveillance and enabling targeted immunotherapies. The hTERT peptide–MHC complex serves as a tumor-specific antigen, making it an attractive target in cancer immunotherapy strategies including TCR-engineered T cells, TCR-like antibodies, and peptide vaccines. Recognition is typically HLA allele-restricted (often HLA-A2 or similar), and the immune response can lead to selective lysis of hTERT-positive cancer cells. The antigen is not entirely tumor-specific, as low-level hTERT expression occurs in certain normal stem cells, leading to a potential but limited risk of off-tumor toxicity. Peptide–MHC complexes such as this one represent a class of immunological targets with high specificity and potential utility in diagnostics, patient monitoring, and therapeutic intervention for a wide range of tumors, and advancing the concept of precision immuno-oncology.

Other names

hTERT peptide/HLA complexTelomerase peptide–MHC complexTelomerase reverse transcriptase peptide–MHC complexTumor-associated peptide–MHC complex (for telomerase)

Recognition by T cell receptor (TCR) on cytotoxic T lymphocytes, leading to immune-mediated cell killing Targeting by TCR-like monoclonal antibodies or cellular therapies engineered to recognize the specific complex, resulting in direct tumor cell lysis Vaccination to elicit endogenous T cell responses to hTERT-derived peptides presented by MHC class I molecules