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Noncognate Interaction with MHC Class II Molecules Is Essential for Maintenance of T Cell Metabolism to Establish Optimal Memory CD4 T Cell Function¹

Alessandra De Riva^*, Christine Bourgeois^*, George Kassiotis and Brigitta Stockinger^2,*

^* Division of Molecular Immunology and Division of Immunoregulation, Medical Research Council Institute for Medical Research, London, United Kingdom

CD4 memory T cells surviving in the absence of MHC class II contact lose their characteristic memory function. To investigate the mechanisms underlying the impaired function of memory T cells in the absence of MHC class II molecules, we analyzed gene expression profiles of resting memory T cells isolated from MHC class II-competent or -deficient hosts. The analysis focused on five transcripts related to T cell activation, metabolism, and survival that are underexpressed in resting memory T cells from MHC class II-deficient hosts compared with MHC class II-competent hosts. CD4 memory cells isolated from MHC class II-deficient hosts display alterations in their degree of differentiation as well as metabolic activity, and these changes are already manifest in the effector phase despite the presence of Ag-expressing dendritic cells. Our data suggest that the absence of interactions with noncognate MHC class II molecules compromises the progressive accumulation of signals that ensure optimal survival and fitness to sustain the metabolic activity of activated T cells and shape the functional capacity of the future memory compartment. Signals via AKT coordinate survival and metabolic pathways and may be one of the crucial events linking interaction with MHC class II molecules to the successful generation of a long-lived functional memory CD4 T cell population.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Medical Research Council U.K.

² Address correspondence and reprint requests to Dr. Brigitta Stockinger, Division of Molecular Immunology, The Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London, U.K. E-mail address: bstocki{at}nimr.mrc.ac.uk

³ Abbreviations used in this paper: DC, dendritic cell; _c, common -chain; PdBu, phorbol dibutyrate.