Clute, Shalyn CatherineWatkin, Levi B.Cornberg, MarkusNaumov, Yuri N.Sullivan, John L.Luzuriaga, KatherineWelsh, Raymond M.Selin, Liisa K.2022-08-232022-08-232005-12-012008-08-27J Clin Invest. 2005 Dec;115(12):3602-12. Epub 2005 Nov 23. <a href="http://dx.doi.org/10.1172/JCI25078">Link to article on publisher's site</a>0021-9738 (Print)10.1172/JCI2507816308574https://hdl.handle.net/20.500.14038/33571The marked proliferation of activated CD8+ T cells is pathognomonic of EBV-associated infectious mononucleosis (IM), common in young adults. Since the diversity and size of the memory CD8+ T cell population increase with age, we questioned whether IM was mediated by the reactivation of memory CD8+ T cells specific to previously encountered pathogens but cross-reactive with EBV. Of 8 HLA-A2+ IM patients, 5 had activated T cells specific to another common virus, as evidenced by a significantly higher number of peripheral blood influenza A virus M1(58-66)-specific T cells compared with healthy immune donors. Two patients with an augmented M1 response had tetramer-defined cross-reactive cells recognizing influenza M1 and EBV-BMLF1(280-288), which accounted for up to one-third of their BMLF1-specific population and likely contributed to a skewed M1-specific T cell receptor repertoire. These epitopes, with only 33% sequence similarity, mediated differential effects on the function of the cross-reactive T cells, which may contribute to alterations in disease outcome. EBV could potentially encode an extensive pool of T cell epitopes that activate other cross-reactive memory T cells. Our results support the concept that cross-reactive memory CD8+ T cells activated by EBV contribute to the characteristic lymphoproliferation of IM.en-USJournal Articlehttps://escholarship.umassmed.edu/gsbs_sp/241606039gsbs_sp/241