Class I negative CD8 T cells reveal the confounding role of peptide-transfer onto CD8 T cells stimulated with soluble H2-K b molecules

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-10, Vol.99 (21), p.13735-13740
• Main Authors: Schott, Eckart, Bertho, Nicolas, Ge, Qing, Maurice, Madelon M., Ploegh, Hidde L.
• Format: Article
• Language: English
• Subjects: Life Sciences
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.212515399

Crosslinking of the T cell receptor has been proposed to be a prerequisite for T cell activation. Although the evidence supports this notion for CD4 T cells, the situation for CD8 T cells is less clear. Soluble class I monomers have been used to determine activation requirements in vitro with contradictory results. The possibility of transfer of peptide from soluble class I molecules onto class I molecules present on the surface of CD8 T cells, with ensuing presentation to other CD8 T cells, has been widely ignored. We show that monomeric and tetrameric class I molecules as well as free peptide can stimulate naïve CD8 T cells in vitro . We generate and characterize CD8 T cells that express the OT-I T cell receptor (for K b /SIINFEKL) yet lack K b and D b molecules, and show that their activation requirements differ from their class I positive counterparts when stimulated with soluble K b molecules. By eliminating the confounding effect of peptide transfer, we unmask the true activation requirements for naïve CD8 T cells and show that multivalent engagement of T cell receptors, as well as costimulation, is required for optimal stimulation.