title: Lack of original antigenic sin in recall CD8(+) T cell responses.
abstract: In the real world, mice and men are not immunologically naive, having been exposed to numerous antigenic challenges. Prior infections sometimes negatively impact the response to a subsequent infection. This can occur in serial infections with pathogens sharing cross-reactive Ags. At the T cell level it has been proposed that preformed memory T cells, which cross-react with low avidity to epitopes presented in subsequent infections, dampen the response of high-avidity T cells. We investigated this with a series of related MHC class-I restricted Ags expressed by bacterial and viral pathogens. In all cases, we find that high-avidity CD8(+) T cell precursors, either naive or memory, massively expand in secondary cross-reactive infections to dominate the response over low-avidity memory T cells. This holds true even when >10% of the CD8(+) T cell compartment consists of memory T cells that cross-react weakly with the rechallenge ligand. Occasionally, memory cells generated by low-avidity stimulation in a primary infection recognize a cross-reactive epitope with high avidity and contribute positively to the response to a second infection. Taken together, our data show that the phenomenon of original antigenic sin does not occur in all heterologous infections.
authors.affiliation: Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Turner
authors.forename: Leo
authors.initials: L
authors.lastname: Lefrançois
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bevan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003429:Cross Reactions; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL