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- Title
MHC I tetramer staining tends to overestimate the number of functionally relevant self‐reactive CD8 T cells in the preimmune repertoire.
- Authors
Pircher, Hanspeter; Pinschewer, Daniel D.; Boehm, Thomas
- Abstract
Previous studies that used peptide‐MHC (pMHC) tetramers (tet) to identify self‐specific T cells have questioned the effectiveness of thymic‐negative selection. Here, we used pMHCI tet to enumerate CD8 T cells specific for the immunodominant gp33 epitope of lymphocytic choriomeningitis virus glycoprotein (GP) in mice transgenically engineered to express high levels of GP as a self‐antigen in the thymus. In GP‐transgenic mice (GP+), monoclonal P14 TCR+ CD8 T cells that express a GP‐specific TCR could not be detected by gp33/Db‐tet staining, indicative of their complete intrathymic deletion. By contrast, in the same GP+ mice, substantial numbers of polyclonal CD8 T cells identifiable by gp33/Db‐tet were present. The gp33‐tet staining profiles of polyclonal T cells from GP+ and GP‐negative (GP−) mice were overlapping, but mean fluorescence intensities were ∼15% lower in cells from GP+ mice. Remarkably, the gp33‐tet+ T cells in GP+ mice failed to clonally expand after lymphocytic choriomeningitis virus infection, whereas those of GP− mice did so. In Nur77GFP‐reporter mice, dose‐dependent responses to gp33 peptide‐induced TCR stimulation revealed that gp33‐tet+ T cells with high ligand sensitivity are lacking in GP+ mice. Hence, pMHCI tet staining identifies self‐specific CD8 T cells but tends to overestimate the number of truly self‐reactive cells.
- Subjects
T cell receptors; T cells; LYMPHOCYTIC choriomeningitis virus; CD8 antigen; VIRUS diseases
- Publication
European Journal of Immunology, 2023, Vol 53, Issue 8, p1
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.202350402