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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Published on: February 28, 2019

Clustering class I MHC modulates sensitivity of T cell recognition

David R Fooksman1, Gigi Kwik Grönvall, Qing Tang

  • 1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 20, 2006
PubMed

T cell recognition of peptide-MHC is highly specific and is sensitive to very low levels of agonist peptide; however, it is unclear how this effect is achieved or regulated. In this study we show that clustering class I MHC molecules on the cell surface of B lymphoblasts enhances their recognition by mouse and human T cells. We increased clustering of MHC I molecules by two methods, cholesterol depletion and direct cross-linking of a dimerizable MHC construct. Imaging showed that both treatments increased the size and intensity of MHC clusters on the cell surface. Enlarged clusters correlated with enhanced lysis and T cell effector function. Enhancements were peptide-specific and greatest at low concentrations of peptide. Clustering MHC class I enhanced recognition of both strong and weak agonists but not null peptide. Our results indicate that the lateral organization of MHC class I on the cell surface can modulate the sensitivity of T cell recognition of agonist peptide.

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