MHC-restricted antigen presentation and clonal T-cell immunity after myocardial infarction: mechanisms, evidence gaps, and therapeutic opportunities

Myocardial infarction (MI) alters the cardiac immune microenvironment through tissue injury, antigen release, and recruitment of innate and adaptive immune cells. Major histocompatibility complex (MHC)-restricted antigen presentation can connect these events to T-cell responses that influence repair or persistent inflammation. This narrative review examines antigen acquisition, initial T-cell priming in cardiac-draining lymph nodes, and subsequent recognition of peptide-MHC complexes within injured myocardium. We integrate these processes with T-cell receptor (TCR) repertoire studies and a spatial framework encompassing the infarct core, border zone, and remote myocardium. Direct experimental evidence for cardiac antigen-specific responses is distinguished from human repertoire associations, findings in other diseases, and proposed mechanisms. In particular, TCR clonal expansion alone does not establish cardiac antigen specificity, and cardiomyocyte antigen display should be separated from professional antigen-presenting cell function. We also consider vascular and lymphatic remodeling, macrophage heterogeneity, and the effects of sex and age. Therapeutic approaches are evaluated by intervention, model, measured outcome, and evidence context, with particular attention to the cardiac risks of immune checkpoint blockade. This framework identifies the experiments needed to connect antigen identity and clonotype function to ventricular remodeling and to assess selective immune interventions after MI.