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After precursor cells arise in the adult bone marrow or fetal liver, they migrate to the thymus where they rearrange their T\u2010cell receptor genes (<jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>) and undergo selection on the basis of their interactions with ligands expressed by thymic stroma and other cells. Those that survive then exit the thymus to populate the peripheral immune compartment, where they patrol the blood and lymphoid systems. The composition of this pre\u2010immune peripheral repertoire is critically important in determining the robustness of an immune response. In both mice and humans, the magnitude and diversity of a response are directly correlated with the frequency of precursor T cells. Equally relevant are the functional characteristics of these lymphocytes. Engagement of a specific antigen to the <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content> activates signaling pathways in the naive T cell that result in cellular proliferation and the acquisition of particular effector functions. A portion of these persist following the resolution of infection and become memory cells. These memory cells can mount a faster and stronger response when they encounter the same antigen at a later time. As the molecular basis for <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content> ligand interaction has become better defined, it is clear that some T cells can recognize multiple distinct ligands and therefore T\u2010cell memory developed by exposure to one ligand may play a significant role in the response to a different antigen. Thus, there is an increasing focus on understanding how exposure to related or unrelated antigens influences the T\u2010cell repertoire and impacts subsequent immunity. In this review, we discuss the issue of <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content> cross\u2010reactivity in the development of memory phenotype <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cells and the implications for pathogen\u2010specific responses. We review both the human and mouse data and discuss the therapeutic implications of these findings in the contexts of infection and vaccination.<\/jats:p>","DOI":"10.1111\/imr.12095","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T05:59:52Z","timestamp":1376632792000},"page":"95-109","source":"Crossref","is-referenced-by-count":45,"title":["Antiviral memory phenotype T cells in unexposed adults"],"prefix":"10.1111","volume":"255","author":[{"given":"Laura F.","family":"Su","sequence":"first","affiliation":[{"name":"The Division of Immunology and Rheumatology Department of Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Davis","sequence":"additional","affiliation":[{"name":"The Institute for Immunity, Transplantation, and Infection Stanford University School of Medicine Stanford CA USA"},{"name":"The Howard Hughes Medical Institute and the Department of Microbiology and Immunology Stanford University School of Medicine Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/334395a0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03547.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2190"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.04.010"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102190"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00093-11"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(98)01299-7"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"3946","DOI":"10.4049\/jimmunol.152.8.3946","article-title":"Use of global amino acid replacements to define the requirements for MHC binding and T cell recognition of moth cytochrome c (93\u2010103)","volume":"152","author":"Reay PA","year":"1994","journal-title":"J Immunol"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020090"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.09.013"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512283332601"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.144.6.1641"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"5000","DOI":"10.4049\/jimmunol.151.9.5000","article-title":"Degenerate recognition of a dissimilar antigenic peptide by myelin basic protein\u2010reactive T cells. 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