title: Competition between T cells maintains clonal dominance during memory inflation induced by MCMV.
abstract: Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus-specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T-cell receptors (TCRs) with high affinity for HCMV-derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT-I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT-I T cells were selectively enriched during the first 3 weeks of infection. Similarly, in the absence of OT-I T cells, the functional avidity of SIINFEKL-specific T cells increased from early to late times postinfection. However, even when exceedingly small numbers of OT-I T cells were transferred, their inflation limited the inflation of host-derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT-I T cells in some mice, which allowed host-derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner.
authors: Department of Microbiology and Immunology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors: Holly
authors: H
authors: Turula
authors: Corinne J
authors: CJ
authors: Smith
authors: Finn
authors: F
authors: Grey
authors: Katherine A
authors: KA
authors: Zurbach
authors: Christopher M
authors: CM
authors: Snyder
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D058948:Cell Tracking; D002999:Clone Cells; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic; D018146:Muromegalovirus; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D013997:Time Factors
chemical_list: D016056:Immunodominant Epitopes; D010455:Peptides; D011948:Receptors, Antigen, T-Cell
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