Positive selection of CD4(+) T cells is induced in vivo by agonist and inhibited by antagonist peptides

• Published in: The Journal of experimental medicine Vol. 194; no. 4; pp. 407 - 416
• Main Authors: Kraj, P, Pacholczyk, R, Ignatowicz, H, Kisielow, P, Jensen, P, Ignatowicz, L
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 20-08-2001
• Subjects: Amino Acid Sequence; Animals; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Mice; Mice, Transgenic; Molecular Sequence Data; Original; Peptides - chemistry; Peptides - pharmacology; Receptors, Antigen, T-Cell, alpha-beta - genetics; Thymus Gland - cytology; Thymus Gland - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.194.4.407

The nature of peptides that positively select T cells in the thymus remains poorly defined. Here we report an in vivo model to study the mechanisms of positive selection of CD4(+) T cells. We have restored positive selection of TCR transgenic CD4(+) thymocytes, arrested at the CD4(+)CD8(+) stage, due to the lack of the endogenously selecting peptide(s), in mice deficient for H2-M and invariant chain. A single injection of soluble agonist peptide(s) initiated positive selection of CD4(+) transgenic T cells that lasted for up to 14 days. Positively selected CD4(+) T cells repopulated peripheral lymphoid organs and could respond to the antigenic peptide. Furthermore, coinjection of the antagonist peptide significantly inhibited agonist-driven positive selection. Hence, contrary to the prevailing view, positive selection of CD4(+) thymocytes can be induced in vivo by agonist peptides and may be a result of accumulation of signals from TCR engaged by different peptides bound to major histocompatibility complex class II molecules. We have also identified a candidate natural agonist peptide that induces positive selection of CD4(+) TCR transgenic thymocytes.