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J Immunol. 2010 Jun 1;184(11):6320-6. doi: 10.4049/jimmunol.1000149. Epub 2010 May 3.

Lack of original antigenic sin in recall CD8(+) T cell responses.

Author information

1
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

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.

PMID:
20439913
PMCID:
PMC2982183
DOI:
10.4049/jimmunol.1000149
[Indexed for MEDLINE]
Free PMC Article

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