Encounters with SARS-CoV-2 antigens provide opportunities to induce and establish productive programs of cellular adaptive immunity in humans. While both prior infection and vaccination protect against severe COVID-19, reported outcomes exhibit substantial immunological and epidemiological heterogeneity. These include the induction of antigen-specific T cells, their longevity and functional profile, and their eventual ability to protect the host from disease. With the growing evidence that these are shaped by early immunological events, we hypothesize that distinct phenotypes of memory T cells arise in natural infection or vaccination. To this end, we profiled transcriptomes, cell surface proteomes and TCRs of Spike-specific T cells selected by AIM from healthy cohorts of mild COVID-19 convalescent and mRNA-vaccinated individuals 6 months after initial antigenic encounter. Additionally, we included a cohort of mRNA-vaccinated donors on TNF inhibitor therapy who demonstrated T cell responses similar in profile to those induced by natural infection. In line with our previous findings, our analysis revealed that the higher frequencies of clonally diverse Spike-specific circulating T cell memory maintained in natural infection is recapitulated in donors vaccinated under TNFi but not healthy vaccinated donors. Moreover, natural infection induces subsets enriched in features of long-lived memory, effector function, Th1 cytokine production and IFN-response signatures, likewise patterned by mRNA-vaccinated donors on TNFi. The similarity in these phenotypes suggest that TNF is a major contributor to the establishment of T cell memory through these routes of immunization.