{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T06:02:53Z","timestamp":1780293773537,"version":"3.54.0"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The adaptive immune system continuously encounters antigens from a wide range of sources, including pathogens, self-tissues, tumors, and environmental agents. While extensive studies have characterized how lymphocytes respond to antigen binding, most experimental frameworks consider the antigenic environment as static. In reality, antigen levels can fluctuate dramatically across a wide range of temporal and spatial scales. In this review, we examine how the dynamics of antigen presentation, ranging from molecular binding events to organism-level exposure, affect T cell activation and fate. We discuss the cellular and molecular mechanisms that allow T cells to detect and respond to changes in antigen concentration over timescales from seconds to days. These include kinetic proofreading of TCR signaling, frequency-dependent decoding in intracellular signaling networks, and population-level feedback circuits involving effector and regulatory T cells. Theoretical and experimental evidence suggests that T cells are tuned not only to antigen quantity but also to its rate of change, with implications for tolerance, immune activation, and memory formation. We highlight how manipulating the dynamics of antigen exposure, such as through controlled vaccine delivery, can modulate immune responses and suggest that incorporating temporal features into immunological models may improve our understanding of immune decision-making and inform therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1806850","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:30:32Z","timestamp":1780291832000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["T cell decision-making decodes the dynamic antigenic landscape"],"prefix":"10.3389","volume":"17","author":[{"given":"Inbal","family":"Eizenberg-Magar","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Dayan","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benny","family":"Chain","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, UCL","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron E.","family":"Antebi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1146\/annurev-immunol-032712-100027","article-title":"Dynamic tuning of lymphocytes: physiological basis, mechanisms, and function","volume":"33","author":"Grossman","year":"2015","journal-title":"Annu Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3521","article-title":"The speed of change: towards a discontinuity theory of immunity","volume":"13","author":"Pradeu","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158013","article-title":"Variability and robustness in T cell activation from regulated heterogeneity in protein levels","volume":"321","author":"Feinerman","year":"2008","journal-title":"Sci (New York NY)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0489-8","article-title":"Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics","volume":"20","author":"Voisinne","year":"2019","journal-title":"Nat Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.01.012","article-title":"The role of T cell receptor signaling thresholds in guiding T cell fate decisions","volume":"33","author":"Zikherman","year":"2015","journal-title":"Curr Opin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900054","article-title":"The impact of TCR-binding properties and antigen presentation format on T cell responsiveness","volume":"183","author":"Chervin","year":"2009","journal-title":"J Immunol (Baltimore Md: 1950)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/advan.00066.2013","article-title":"T cell responses: naive to memory and everything in between","volume":"37","author":"Pennock","year":"2013","journal-title":"Adv Physiol Educ"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.7554\/elife.01944","article-title":"T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks","volume":"3","author":"Tkach","year":"2014","journal-title":"eLife"},{"key":"B9","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3390\/cancers8030036","article-title":"Different subsets of T cells, memory, effector functions, and CAR-T immunotherapy","volume":"8","author":"Golubovskaya","year":"2016","journal-title":"Cancers"},{"key":"B10","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1006\/smim.2000.0232","article-title":"Self-tolerance: context dependent tuning of T cell antigen recognition","volume":"12","author":"Grossman","year":"2000","journal-title":"Semin Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260044","article-title":"T cell signaling. 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