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

P. Kraj, R. Pacholczyk, H. Ignatowicz, P. Kisielow, P. Jensen, L. Ignatowicz

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)407-416
Number of pages10
JournalJournal of Experimental Medicine
Volume194
Issue number4
DOIs
StatePublished - Aug 20 2001

Fingerprint

Peptides
Thymocytes
T-Lymphocytes
Major Histocompatibility Complex
Thymus Gland
Injections

Keywords

  • Agonist peptide
  • CD4 cells
  • MHC class II
  • Positive selection
  • Thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Positive selection of CD4+ t cells is induced in vivo by agonist and inhibited by antagonist peptides. / Kraj, P.; Pacholczyk, R.; Ignatowicz, H.; Kisielow, P.; Jensen, P.; Ignatowicz, L.

In: Journal of Experimental Medicine, Vol. 194, No. 4, 20.08.2001, p. 407-416.

Research output: Contribution to journalArticle

Kraj, P. ; Pacholczyk, R. ; Ignatowicz, H. ; Kisielow, P. ; Jensen, P. ; Ignatowicz, L. / Positive selection of CD4+ t cells is induced in vivo by agonist and inhibited by antagonist peptides. In: Journal of Experimental Medicine. 2001 ; Vol. 194, No. 4. pp. 407-416.
@article{956099a132e649179ad5a3e12dbcad7d,
title = "Positive selection of CD4+ t cells is induced in vivo by agonist and inhibited by antagonist peptides",
abstract = "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.",
keywords = "Agonist peptide, CD4 cells, MHC class II, Positive selection, Thymus",
author = "P. Kraj and R. Pacholczyk and H. Ignatowicz and P. Kisielow and P. Jensen and L. Ignatowicz",
year = "2001",
month = "8",
day = "20",
doi = "10.1084/jem.194.4.407",
language = "English (US)",
volume = "194",
pages = "407--416",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "4",

}

TY - JOUR

T1 - Positive selection of CD4+ t cells is induced in vivo by agonist and inhibited by antagonist peptides

AU - Kraj, P.

AU - Pacholczyk, R.

AU - Ignatowicz, H.

AU - Kisielow, P.

AU - Jensen, P.

AU - Ignatowicz, L.

PY - 2001/8/20

Y1 - 2001/8/20

N2 - 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.

AB - 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.

KW - Agonist peptide

KW - CD4 cells

KW - MHC class II

KW - Positive selection

KW - Thymus

UR - http://www.scopus.com/inward/record.url?scp=0035920562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035920562&partnerID=8YFLogxK

U2 - 10.1084/jem.194.4.407

DO - 10.1084/jem.194.4.407

M3 - Article

C2 - 11514598

AN - SCOPUS:0035920562

VL - 194

SP - 407

EP - 416

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 4

ER -