Positive selection of CD4(+) T cells is induced in vivo by agonist and inhibited by antagonist peptides.
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.
Kraj
P
P
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Pacholczyk
R
R
Ignatowicz
H
H
Kisielow
P
P
Jensen
P
P
Ignatowicz
L
L
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta