Mature T cell reactivity altered by peptide agonist that induces positive selection.
J Exp Med
; 183(3): 1093-104, 1996 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-8642251
ABSTRACT
Recent studies have investigated how defined peptides influence T cell development. Using a T cell receptor-transgenic beta2-microglobulin-deficient model, we have examined T cell maturation in fetal thymic organ cultures in the presence of various peptides containing single-alanine substitutions of the strong peptide agonist, p33. Cocultivation with the peptide A4Y, which contains an altered T cell contact residue, resulted in efficient positive selection. Several in vitro assays demonstrated that A4Y was a moderate agonist relative to p33. Although A4Y promoted positive selection over a wide concentration range, high doses of this peptide could not induce clonal deletion. Thymocytes maturing in the presence of A4Y were no longer able to respond to A4Y, but could proliferate against p33. These studies demonstrate that (a) peptides that induce efficient positive selection at high concentrations are not exclusively antagonists; (b) some agonists do not promote clonal deletion; (c) positive selection requires a unique T cell receptor-peptide-major histocompatibility complex interaction; and (d) interactions with selecting peptides during T cell ontogeny may define the functional reactivity of mature T cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Timo
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Linfócitos T
Limite:
Animals
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article