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PNAS 99 (21): 13729-13734

Copyright © 2002 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / IMMUNOLOGY

Soluble peptide–MHC monomers cause activation of CD8+ T cells through transfer of the peptide to T cell MHC molecules

Qing Ge*,{dagger}, Jennifer D. Stone{dagger},{ddagger}, M. Todd Thompson{ddagger}, Jennifer R. Cochran{ddagger}, Mia Rushe{ddagger}, Herman N. Eisen*, Jianzhu Chen*, and Lawrence J. Stern{ddagger},§,¶

Departments of *Biology, Center for Cancer Research, and {ddagger}Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; and §Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655

Contributed by Herman N. Eisen

Accepted for publication August 26, 2002.

Abstract: T cell receptor (TCR)-mediated activation of CD4+ T cells is known to require multivalent engagement of the TCR by, for example, oligomeric peptide–MHC complexes. In contrast, for CD8+ T cells, there is evidence for TCR-mediated activation by univalent engagement of the TCR. We have here compared oligomeric and monomeric Ld and Kb peptide–MHC complexes and free peptide as stimulators of CD8+ T cells expressing the 2C TCR. We found that the monomers are indeed effective in activating naïve and effector CD8+ T cells, but through an unexpected mechanism that involves transfer of peptide from soluble monomers to T cell endogenous MHC (Kb) molecules. The result is that T cells, acting as antigen-presenting cells, are able to activate other naïve T cells.

Key Words: CD8+ T lymphocytes||T cell receptor||major histocompatibility complex||antigen presentation||lymphocyte activation

{dagger} Q.G. and J.D.S. contributed equally to this work.

To whom correspondence should be addressed. E-mail: lawrence.stern{at}umassmed.edu.

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