title: In vivo modulation of avidity in highly sensitive CD8(+) effector T cells following viral infection.
abstract: Numerous studies have demonstrated a critical role for T cell avidity in predicting in vivo efficacy. Even though the measurement of avidity is now a routine assessment for the analysis of effector and memory T cell populations, our understanding of how this property is controlled in vivo at both the population and individual cell levels is limited. Our previous studies have identified high avidity as a property of the initial effector population generated in mice following respiratory virus infection. As the response progresses, lower avidity cells appear in the effector pool. The studies described here investigate the mechanistic basis of this in vivo regulation of avidity. We present data supporting in vivo avidity modulation within the early high avidity responders that results in a population of lower avidity effector cells. Changes in avidity were correlated with decreased lck expression and increased sensitivity to lck inhibitors in effector cells present at late versus early times postinfection. The possibility of tuning within select individual effectors is a previously unappreciated mechanism for the control of avidity in vivo.
authors: Department of Microbiology and Immunology, Wake Forest University School of Medicine , Winston-Salem, North Carolina.
authors: Beth C
authors: BC
authors: Holbrook
authors: Rama D
authors: RD
authors: Yammani
authors: Lance K
authors: LK
authors: Blevins
authors: Martha A
authors: MA
authors: Alexander-Miller
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D045402:Parainfluenza Virus 5 / Q000276:immunology*; D011485:Protein Binding; D019351:Rubulavirus Infections / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D053645:Interleukin-2 Receptor alpha Subunit; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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