Characterization of a peptide analog of a determinant of type II collagen that suppresses collagen-induced arthritis

Linda Myers, Bo Tang, E. F. Rosloniec, John Stuart, T. M. Chiang, Andrew Kang

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Immunization of susceptible strains of mice with type II collagen (CII) elicits an autoimmune arthritis known as collagen-induced arthritis (CIA). One analogue peptide of the immunodominant T cell determinant, A9 (CII245-270 (I260 → A, A261 → B, F263 → N)), was previously shown to induce a profound suppression of CIA when coadministered at the time of immunization with CII. In the present study, A9 peptide was administered i.p., orally, intranasally, or i.v. 2 to 4 wk following CII immunization. We found that arthritis was significantly suppressed even when A9 was administered after disease was induced. To determine the mechanism of action of A9, cytokine responses to A9 and wild-type peptide A2 by CII- sensitized spleen cells were compared. An increase in IL-4 and IL-10, but not in IFN-γ, was found in A9 culture supernatants. Additionally, cells obtained from A9-immunized mice produced higher amounts of IL-4 and IL-10 when cultured with CII compared with cells obtained from mice immunized with A2, which produced predominantly IFN-γ. Suppression of arthritis could be transferred to naive mice using A9-immune splenocytes. Lastly, phosphorylation of TCRζ was not altered in the immunoprecipitates from the lysates of cells exposed to analogue peptides (A9 and A10) together with wild-type A2 in a T cell line and two I-A(q)-restricted, CII-specific T hybridomas. We conclude that analogue peptide A9 is effective in suppressing established CIA by inducing T cells to produce a Th2 cytokine pattern in response to CII.

Original languageEnglish (US)
Pages (from-to)3589-3595
Number of pages7
JournalJournal of Immunology
Volume161
Issue number7
StatePublished - Oct 1 1998

Fingerprint

Experimental Arthritis
Collagen Type II
varespladib methyl
Arthritis
Immunization
Peptides
T-Lymphocytes
Interleukin-4
Interleukin-10
Cytokines
Peptide T
antineoplaston A10
Hybridomas
Spleen
Phosphorylation
Cell Line

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Characterization of a peptide analog of a determinant of type II collagen that suppresses collagen-induced arthritis. / Myers, Linda; Tang, Bo; Rosloniec, E. F.; Stuart, John; Chiang, T. M.; Kang, Andrew.

In: Journal of Immunology, Vol. 161, No. 7, 01.10.1998, p. 3589-3595.

Research output: Contribution to journalArticle

Myers, Linda ; Tang, Bo ; Rosloniec, E. F. ; Stuart, John ; Chiang, T. M. ; Kang, Andrew. / Characterization of a peptide analog of a determinant of type II collagen that suppresses collagen-induced arthritis. In: Journal of Immunology. 1998 ; Vol. 161, No. 7. pp. 3589-3595.
@article{4a14a9ba067848efaf830351f8ab2663,
title = "Characterization of a peptide analog of a determinant of type II collagen that suppresses collagen-induced arthritis",
abstract = "Immunization of susceptible strains of mice with type II collagen (CII) elicits an autoimmune arthritis known as collagen-induced arthritis (CIA). One analogue peptide of the immunodominant T cell determinant, A9 (CII245-270 (I260 → A, A261 → B, F263 → N)), was previously shown to induce a profound suppression of CIA when coadministered at the time of immunization with CII. In the present study, A9 peptide was administered i.p., orally, intranasally, or i.v. 2 to 4 wk following CII immunization. We found that arthritis was significantly suppressed even when A9 was administered after disease was induced. To determine the mechanism of action of A9, cytokine responses to A9 and wild-type peptide A2 by CII- sensitized spleen cells were compared. An increase in IL-4 and IL-10, but not in IFN-γ, was found in A9 culture supernatants. Additionally, cells obtained from A9-immunized mice produced higher amounts of IL-4 and IL-10 when cultured with CII compared with cells obtained from mice immunized with A2, which produced predominantly IFN-γ. Suppression of arthritis could be transferred to naive mice using A9-immune splenocytes. Lastly, phosphorylation of TCRζ was not altered in the immunoprecipitates from the lysates of cells exposed to analogue peptides (A9 and A10) together with wild-type A2 in a T cell line and two I-A(q)-restricted, CII-specific T hybridomas. We conclude that analogue peptide A9 is effective in suppressing established CIA by inducing T cells to produce a Th2 cytokine pattern in response to CII.",
author = "Linda Myers and Bo Tang and Rosloniec, {E. F.} and John Stuart and Chiang, {T. M.} and Andrew Kang",
year = "1998",
month = "10",
day = "1",
language = "English (US)",
volume = "161",
pages = "3589--3595",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Characterization of a peptide analog of a determinant of type II collagen that suppresses collagen-induced arthritis

AU - Myers, Linda

AU - Tang, Bo

AU - Rosloniec, E. F.

AU - Stuart, John

AU - Chiang, T. M.

AU - Kang, Andrew

PY - 1998/10/1

Y1 - 1998/10/1

N2 - Immunization of susceptible strains of mice with type II collagen (CII) elicits an autoimmune arthritis known as collagen-induced arthritis (CIA). One analogue peptide of the immunodominant T cell determinant, A9 (CII245-270 (I260 → A, A261 → B, F263 → N)), was previously shown to induce a profound suppression of CIA when coadministered at the time of immunization with CII. In the present study, A9 peptide was administered i.p., orally, intranasally, or i.v. 2 to 4 wk following CII immunization. We found that arthritis was significantly suppressed even when A9 was administered after disease was induced. To determine the mechanism of action of A9, cytokine responses to A9 and wild-type peptide A2 by CII- sensitized spleen cells were compared. An increase in IL-4 and IL-10, but not in IFN-γ, was found in A9 culture supernatants. Additionally, cells obtained from A9-immunized mice produced higher amounts of IL-4 and IL-10 when cultured with CII compared with cells obtained from mice immunized with A2, which produced predominantly IFN-γ. Suppression of arthritis could be transferred to naive mice using A9-immune splenocytes. Lastly, phosphorylation of TCRζ was not altered in the immunoprecipitates from the lysates of cells exposed to analogue peptides (A9 and A10) together with wild-type A2 in a T cell line and two I-A(q)-restricted, CII-specific T hybridomas. We conclude that analogue peptide A9 is effective in suppressing established CIA by inducing T cells to produce a Th2 cytokine pattern in response to CII.

AB - Immunization of susceptible strains of mice with type II collagen (CII) elicits an autoimmune arthritis known as collagen-induced arthritis (CIA). One analogue peptide of the immunodominant T cell determinant, A9 (CII245-270 (I260 → A, A261 → B, F263 → N)), was previously shown to induce a profound suppression of CIA when coadministered at the time of immunization with CII. In the present study, A9 peptide was administered i.p., orally, intranasally, or i.v. 2 to 4 wk following CII immunization. We found that arthritis was significantly suppressed even when A9 was administered after disease was induced. To determine the mechanism of action of A9, cytokine responses to A9 and wild-type peptide A2 by CII- sensitized spleen cells were compared. An increase in IL-4 and IL-10, but not in IFN-γ, was found in A9 culture supernatants. Additionally, cells obtained from A9-immunized mice produced higher amounts of IL-4 and IL-10 when cultured with CII compared with cells obtained from mice immunized with A2, which produced predominantly IFN-γ. Suppression of arthritis could be transferred to naive mice using A9-immune splenocytes. Lastly, phosphorylation of TCRζ was not altered in the immunoprecipitates from the lysates of cells exposed to analogue peptides (A9 and A10) together with wild-type A2 in a T cell line and two I-A(q)-restricted, CII-specific T hybridomas. We conclude that analogue peptide A9 is effective in suppressing established CIA by inducing T cells to produce a Th2 cytokine pattern in response to CII.

UR - http://www.scopus.com/inward/record.url?scp=0032194109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032194109&partnerID=8YFLogxK

M3 - Article

VL - 161

SP - 3589

EP - 3595

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -