Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides

A. Gaszewska-Mastalarz, P. Muranski, B. Chmielowski, P. Kraj, Leszek Ignatowicz

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We have investigated the development of CD4+ T cells in mice expressing low levels of transgenic class II MHC molecules (A(b)) preoccupied with covalent peptide (Ep), which in the presence of invariant chain (Ii) is extensively cleaved and replaced with self-derived peptides. In these mice, the transgenic A(b) molecules, bound with predominant peptide (Ep) and with multiple self-peptides, selected more CD4+ T cells than A(b)/self-peptide complexes expressed in wild-type mice. The enhanced outcome of thymic selection was a result of impaired negative selection, rather than more efficient positive selection by an overall lowered abundance of self-derived A(b)/peptide complexes. Peripheral CD4+ T cells in the A(b)EpIi+ mice had memory phenotype, often followed by polyclonal activation of B cells. The A(b)EpIi+ mice preserved their good health and had a normal life span despite the profound number of activated CD4+ T cells and B cells in peripheral lymphoid organs, moderate hypergammaglobulinemia, and deposited complexes in the kidneys. We propose that CD4+ T cells positively selected due to low avidity for high abundant A(b)Ep complex avoid negative selection on A(b) molecules loaded with low abundant peptides and become self-reactive in the peripheral lymphoid organs.

Original languageEnglish (US)
Pages (from-to)6099-6106
Number of pages8
JournalJournal of Immunology
Volume165
Issue number11
DOIs
StatePublished - Dec 1 2000

Fingerprint

T-Lymphocytes
Peptides
B-Lymphocytes
Hypergammaglobulinemia
Transgenic Mice
Phenotype
Kidney
Health

ASJC Scopus subject areas

  • Immunology

Cite this

Gaszewska-Mastalarz, A., Muranski, P., Chmielowski, B., Kraj, P., & Ignatowicz, L. (2000). Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides. Journal of Immunology, 165(11), 6099-6106. https://doi.org/10.4049/jimmunol.165.11.6099

Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides. / Gaszewska-Mastalarz, A.; Muranski, P.; Chmielowski, B.; Kraj, P.; Ignatowicz, Leszek.

In: Journal of Immunology, Vol. 165, No. 11, 01.12.2000, p. 6099-6106.

Research output: Contribution to journalArticle

Gaszewska-Mastalarz, A, Muranski, P, Chmielowski, B, Kraj, P & Ignatowicz, L 2000, 'Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides', Journal of Immunology, vol. 165, no. 11, pp. 6099-6106. https://doi.org/10.4049/jimmunol.165.11.6099
Gaszewska-Mastalarz, A. ; Muranski, P. ; Chmielowski, B. ; Kraj, P. ; Ignatowicz, Leszek. / Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides. In: Journal of Immunology. 2000 ; Vol. 165, No. 11. pp. 6099-6106.
@article{e6d60a93cb4949639427e5afa04267db,
title = "Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides",
abstract = "We have investigated the development of CD4+ T cells in mice expressing low levels of transgenic class II MHC molecules (A(b)) preoccupied with covalent peptide (Ep), which in the presence of invariant chain (Ii) is extensively cleaved and replaced with self-derived peptides. In these mice, the transgenic A(b) molecules, bound with predominant peptide (Ep) and with multiple self-peptides, selected more CD4+ T cells than A(b)/self-peptide complexes expressed in wild-type mice. The enhanced outcome of thymic selection was a result of impaired negative selection, rather than more efficient positive selection by an overall lowered abundance of self-derived A(b)/peptide complexes. Peripheral CD4+ T cells in the A(b)EpIi+ mice had memory phenotype, often followed by polyclonal activation of B cells. The A(b)EpIi+ mice preserved their good health and had a normal life span despite the profound number of activated CD4+ T cells and B cells in peripheral lymphoid organs, moderate hypergammaglobulinemia, and deposited complexes in the kidneys. We propose that CD4+ T cells positively selected due to low avidity for high abundant A(b)Ep complex avoid negative selection on A(b) molecules loaded with low abundant peptides and become self-reactive in the peripheral lymphoid organs.",
author = "A. Gaszewska-Mastalarz and P. Muranski and B. Chmielowski and P. Kraj and Leszek Ignatowicz",
year = "2000",
month = "12",
day = "1",
doi = "10.4049/jimmunol.165.11.6099",
language = "English (US)",
volume = "165",
pages = "6099--6106",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides

AU - Gaszewska-Mastalarz, A.

AU - Muranski, P.

AU - Chmielowski, B.

AU - Kraj, P.

AU - Ignatowicz, Leszek

PY - 2000/12/1

Y1 - 2000/12/1

N2 - We have investigated the development of CD4+ T cells in mice expressing low levels of transgenic class II MHC molecules (A(b)) preoccupied with covalent peptide (Ep), which in the presence of invariant chain (Ii) is extensively cleaved and replaced with self-derived peptides. In these mice, the transgenic A(b) molecules, bound with predominant peptide (Ep) and with multiple self-peptides, selected more CD4+ T cells than A(b)/self-peptide complexes expressed in wild-type mice. The enhanced outcome of thymic selection was a result of impaired negative selection, rather than more efficient positive selection by an overall lowered abundance of self-derived A(b)/peptide complexes. Peripheral CD4+ T cells in the A(b)EpIi+ mice had memory phenotype, often followed by polyclonal activation of B cells. The A(b)EpIi+ mice preserved their good health and had a normal life span despite the profound number of activated CD4+ T cells and B cells in peripheral lymphoid organs, moderate hypergammaglobulinemia, and deposited complexes in the kidneys. We propose that CD4+ T cells positively selected due to low avidity for high abundant A(b)Ep complex avoid negative selection on A(b) molecules loaded with low abundant peptides and become self-reactive in the peripheral lymphoid organs.

AB - We have investigated the development of CD4+ T cells in mice expressing low levels of transgenic class II MHC molecules (A(b)) preoccupied with covalent peptide (Ep), which in the presence of invariant chain (Ii) is extensively cleaved and replaced with self-derived peptides. In these mice, the transgenic A(b) molecules, bound with predominant peptide (Ep) and with multiple self-peptides, selected more CD4+ T cells than A(b)/self-peptide complexes expressed in wild-type mice. The enhanced outcome of thymic selection was a result of impaired negative selection, rather than more efficient positive selection by an overall lowered abundance of self-derived A(b)/peptide complexes. Peripheral CD4+ T cells in the A(b)EpIi+ mice had memory phenotype, often followed by polyclonal activation of B cells. The A(b)EpIi+ mice preserved their good health and had a normal life span despite the profound number of activated CD4+ T cells and B cells in peripheral lymphoid organs, moderate hypergammaglobulinemia, and deposited complexes in the kidneys. We propose that CD4+ T cells positively selected due to low avidity for high abundant A(b)Ep complex avoid negative selection on A(b) molecules loaded with low abundant peptides and become self-reactive in the peripheral lymphoid organs.

UR - http://www.scopus.com/inward/record.url?scp=0034541172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034541172&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.165.11.6099

DO - 10.4049/jimmunol.165.11.6099

M3 - Article

VL - 165

SP - 6099

EP - 6106

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -