The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/9/1083/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 6, September 21, 1998 1083-1089

Articles

Antagonist Peptide Selects Thymocytes Expressing a Class II Major Histocompatibility Complex–restricted T Cell Receptor into the CD8 Lineage

Ariane Volkmann*, Thomas Barthlott*, Siegfried Weiss{ddagger}, Ronald Frank{ddagger}, and Brigitta Stockinger*

From the * Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom; and {ddagger} Gesellschaft für Biotechnologische Forschung, D-38124 Braunschweig, Germany

CD4/CD8 lineage decision is an important event during T cell maturation in the thymus. CD8 T cell differentiation usually requires corecognition of major histocompatibility complex (MHC) class I by the T cell receptor (TCR) and CD8, whereas CD4 T cells differentiate as a consequence of MHC class II recognition by the TCR and CD4. The involvement of specific peptides in the selection of T cells expressing a particular TCR could be demonstrated so far for the CD8 lineage only. We used mice transgenic for an MHC class II-restricted TCR to investigate the role of antagonistic peptides in CD4 T cell differentiation. Interestingly, antagonists blocked the development of CD4+ cells that normally differentiate in thymus organ culture from those mice, and they induced the generation of CD8+ cells in thymus organ culture from mice impaired in CD4+ cell development (invariant chain–deficient mice). These results are in line with recent observations that antagonistic signals direct differentiation into the CD8 lineage, regardless of MHC specificity.

Key Words: antagonist • major histocompatibility complex • thymocyte differentiation • thymic selection • T cell receptor

Address correspondence to Brigitta Stockinger, Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Phone: 44-181-959-3666; Fax: 44-181-913-8531; E-mail: b-stocki{at}nimr.mrc.ac.uk

Ariane Volkmann's present address is Division of Immunology, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720.

Abbreviations used: HSA, heat-stable antigen; NTOC, neonatal thymic lobes.


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