One of the First Studies Using Peptide:MHC Class I Tetramers

Essay

One of the first studies using peptide:MHC class I tetramers to measure the frequencies of virus-specific CD8 T cells in an acute virus infection in mice demonstrated the remarkable finding that more than 50% of all the CD8 T cells in the mouse were virus-specific at the peak of the response (day 8 post-infection). This study used the virus lymphocytic choriomeningitis virus (LCMV). One peptide:MHC tetramer used in this study, H-2-D^b loaded with the LCMV nucleoprotein peptide NP_396-404, bound to ~20% of the CD8 T cells in the spleen at day 8 post-infection. Why did this tetramer only stain ~20% of the CD8 T cells if more than half of the CD8 cells in the spleen were virus-specific?