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Elucidating the relationships between a class I peptide antigen, a CD8 T cell receptor (TCR) specific to that antigen, and the T cell phenotype that emerges following antigen stimulation, remains a mostly unsolved problem, largely due to the lack of large data sets that can be mined to resolve such relationships. Here, we describe Antigen-TCR Pairing and Multiomic Analysis of T-cells (APMAT), an integrated experimental-computational framework designed for the high-throughput capture and analysis of CD8 T cells, with paired antigen, TCR sequence, and single-cell transcriptome. Starting with 951 putative antigens representing a comprehensive survey of the SARS-CoV-2 viral proteome, we utilize APMAT for the capture and single cell analysis of CD8 T cells from 62 HLA A*02:01 COVID-19 participants. We leverage this unique, comprehensive dataset to integrate with peptide antigen properties, TCR CDR3 sequences, and T cell phenotypes to show that distinct physicochemical features of the antigen-TCR pairs strongly associate with both T cell phenotype and T cell persistence. This analysis suggests that CD8+ T cell phenotype following antigen stimulation is at least partially deterministic, rather than the result of stochastic biological properties., Competing Interests: Competing Interests Statement J.R.H. is a consultant to Regeneron, and has received research support from Gilead and Merck. J.D.G. declared contracted research with Gilead, Lilly, and Regeneron. P.D.G. is on the Scientific Advisory Board of Affini-T, Catalio, Earli, Elpiscience, Fibrogen, Immunoscape, Metagenomi, Nextech, and Rapt; was a scientific founder of Juno Therapeutics and Affini-T; and receives research support from Lonza and Affini-T Therapeutics. H.C. reported consulting with Ellume, Pfizer, and the Bill and Melinda Gates Foundation and has served on advisory boards for Vir, Merck and Abbvie. H.C. has conducted CME teaching with Medscape, Vindico, Cataylst CME, and Clinical Care Options. H.C. has received research funding from Gates Ventures, and support and reagents from Ellume and Cepheid outside of the submitted work. The remaining authors declare no competing interests.