Senescent cell-associated antigens presented on MHC to T-cell receptors (SAA)

Senescent cell-associated antigens (SAAs) are specific peptides or proteins presented on the Major Histocompatibility Complex (MHC) of senescent cells, which are recognized by T-cell receptors (TCRs) to trigger an adaptive immune response [1.3.1, 1.3.2]. Cellular senescence is a state of permanent cell cycle arrest induced by stressors like DNA damage or oncogene activation, characterized by the secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP) [1.1.2, 1.4.3]. While senescent cells are normally cleared by the immune system, their accumulation with age contributes to chronic inflammation and various age-related diseases, including cancer, fibrosis, and cardiovascular disorders [1.4.1, 1.5.3]. Targeting these MHC-presented antigens allows for the development of "seno-immunotherapies," such as TCR-engineered T cells or vaccines, designed to selectively eliminate senescent cells while sparing healthy tissue [1.2.1, 1.2.3]. Recent research has identified unique immunopeptidomes in senescent cells, where approximately 10% of MHC-I epitopes are unique to the senescent state, offering a precise therapeutic window for treating age-associated pathologies and enhancing anti-tumor immunity [1.1.1, 1.3.1]. Experimental therapies currently in development include CAR-T cells targeting surface markers like uPAR and GPNMB, as well as vaccines and TCR-T cells targeting internal proteins presented as MHC-bound peptides [1.2.3, 1.5.5].

Other names

Senescence-associated antigensSenescence-associated neoantigensAging-associated antigensSenescence-associated MHC-peptidesSenescence-associated self-peptides

Selective elimination of senescent cells through T-cell mediated cytotoxicity (CD8+ or CD4+) following the recognition of specific peptides presented on Major Histocompatibility Complex (MHC) molecules by T-cell receptors (TCRs).