T cell receptor complementarity determining region 3 length analysis reveals the absence of a characteristic public T cell repertoire in neonatal tolerance

The response in the 'tolerant' mouse within the residual repertoire is quantitatively similar but qualitatively different

Emanual Michael Maverakis, Jonathan T. Beech, Stephen S. Wilson, Anthony Quinn, Brian Pedersen, Eli E. Sercarz

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24 Citations (Scopus)

Abstract

All adult BALB/c mice immunized with hen egg white lysozyme (HEL) or its dominant determinant, peptide (p)106-116, mount a T cell response using a 'public' vβ8.2Jβ1.5 T cell clone. Neonatal exposure to tolerance-inducing doses of antigen can drastically diminish responsiveness in the draining lymph nodes but not in the spleens of animals challenged as adults with the cognate antigen. To determine the role oft cell deletion or anergy within the mechanisms of observed neonatal 'tolerance,' we treated neonatal BALB/c mice with HEL and directly followed the characteristic public clone using complementarity determining region 3 length T cell repertoire analysis. Our results confirm that despite intraperitoneal injection of neonates with a high dose of HEL emulsified in incomplete Freund's adjuvant, a strong splenic proliferative response to HEL was observed upon recall. However, the adult splenic T cell response of these neonatally treated mice lacked the usual Vβ8.2Jβ1.5 public clone characteristic of HEL-primed BALB/c mice. After challenge with HEL-complete Freund's adjuvant as adults, immunoglobulin (Ig)G2a isotype antibody was drastically reduced, and IgG1 was found to be the predominant anti-HEL IgG isotype expressed, indicating a deviation of cytokine response toward T helper type 2. 5-wk-old mice, nasally instilled with tolerogenic doses of HEL p106-116, also showed significant inhibition of this public T cell expansion. These results demonstrate that during neonatal and adult nasal tolerance induction, deletion/anergy removes the public clone, exposing a response of similar specificity but that is characterized by the T helper type 2 phenotype and a splenic residence.

Original languageEnglish (US)
Pages (from-to)695-702
Number of pages8
JournalJournal of Experimental Medicine
Volume191
Issue number4
DOIs
StatePublished - Feb 21 2000

Fingerprint

Complementarity Determining Regions
Egg White
T-Cell Antigen Receptor
T-Lymphocytes
Clone Cells
Immunoglobulin G
Antigens
Freund's Adjuvant
hen egg lysozyme
Immunoglobulin Isotypes
Intraperitoneal Injections
Nose
Spleen
Lymph Nodes
Cytokines
Phenotype
Antibodies

Keywords

  • Deletion/anergy
  • HEL
  • Nasal instillation
  • Neonatal tolerance
  • T cell repertoire

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "T cell receptor complementarity determining region 3 length analysis reveals the absence of a characteristic public T cell repertoire in neonatal tolerance: The response in the 'tolerant' mouse within the residual repertoire is quantitatively similar but qualitatively different",
abstract = "All adult BALB/c mice immunized with hen egg white lysozyme (HEL) or its dominant determinant, peptide (p)106-116, mount a T cell response using a 'public' vβ8.2Jβ1.5 T cell clone. Neonatal exposure to tolerance-inducing doses of antigen can drastically diminish responsiveness in the draining lymph nodes but not in the spleens of animals challenged as adults with the cognate antigen. To determine the role oft cell deletion or anergy within the mechanisms of observed neonatal 'tolerance,' we treated neonatal BALB/c mice with HEL and directly followed the characteristic public clone using complementarity determining region 3 length T cell repertoire analysis. Our results confirm that despite intraperitoneal injection of neonates with a high dose of HEL emulsified in incomplete Freund's adjuvant, a strong splenic proliferative response to HEL was observed upon recall. However, the adult splenic T cell response of these neonatally treated mice lacked the usual Vβ8.2Jβ1.5 public clone characteristic of HEL-primed BALB/c mice. After challenge with HEL-complete Freund's adjuvant as adults, immunoglobulin (Ig)G2a isotype antibody was drastically reduced, and IgG1 was found to be the predominant anti-HEL IgG isotype expressed, indicating a deviation of cytokine response toward T helper type 2. 5-wk-old mice, nasally instilled with tolerogenic doses of HEL p106-116, also showed significant inhibition of this public T cell expansion. These results demonstrate that during neonatal and adult nasal tolerance induction, deletion/anergy removes the public clone, exposing a response of similar specificity but that is characterized by the T helper type 2 phenotype and a splenic residence.",
keywords = "Deletion/anergy, HEL, Nasal instillation, Neonatal tolerance, T cell repertoire",
author = "Maverakis, {Emanual Michael} and Beech, {Jonathan T.} and Wilson, {Stephen S.} and Anthony Quinn and Brian Pedersen and Sercarz, {Eli E.}",
year = "2000",
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doi = "10.1084/jem.191.4.695",
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T2 - The response in the 'tolerant' mouse within the residual repertoire is quantitatively similar but qualitatively different

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AU - Beech, Jonathan T.

AU - Wilson, Stephen S.

AU - Quinn, Anthony

AU - Pedersen, Brian

AU - Sercarz, Eli E.

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