Complementation between HLA-DR4 (DRB1*0401) and specific H2-A molecule in transgenic mice leads to collagen-induced arthritis

Shuchong Pan, Veena D Taneja, Marie M. Griffiths, Harvinder Luthra, Chella S. David

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We generated transgenic mice with DRB1*0401 gene with mutation in the β2 domain (aa 110 and 139) for better interaction with mCD4. The DR4 transgene was introduced into H2-A(q) (B10RQB3) and H2-A(f)(B10RFB3) to examine the role of DR4 in collagen arthritis. The HLA-DR molecules in these mice were found to be functional on the basis of their positive/negative selection of the Vβ T cell repertoire. H2-A(q) mice are resistant to porcine CII-induced arthritis. The RQB3/DR4 mice (H2A(q)/DR4) developed severe collagen induced arthritis (CIA) when immunized with Porcine type II collagen while the negative littermates were resistant. RQB3.DR4 mice were also highly susceptible to CIA induced by Human CII while negative littermates got only mild disease. However, RFB3/DR4 mice (H2A(f)/DR4) did not get CIA with any type II collagen. Therefore, the DR4 gene in the context of H2-A(q) predisposes to severe arthritis but not in the context of H2-Af. Antibodies to renatured cyanogen bromide (CB) cleaved fragments of PII in RQB3/DR4 mice and negative littermates suggest that the presence of DR4 does not result in any differences in specificity of antibody response to CB fragments. These results indicate that a specific gene complementation occurring between DR4 and H2.A(q) but not DR4 and H2A(f) promotes the induction of arthritis with PII and HII in these mice. A similar interaction may be involved between DR and DQ molecules in human RA.

Original languageEnglish (US)
Pages (from-to)816-825
Number of pages10
JournalHuman Immunology
Volume60
Issue number9
DOIs
StatePublished - 1999

Fingerprint

HLA-DR4 Antigen
Experimental Arthritis
Transgenic Mice
Arthritis
Cyanogen Bromide
Collagen Type II
Swine
Genes
HLA-DR Antigens
HLA-DRB1*04:01 antigen
Transgenes
Antibody Formation
T-Lymphocytes
Mutation
Antibodies

Keywords

  • In vivo model
  • MHC
  • Rheumatoid arthritis
  • Transgenic

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Complementation between HLA-DR4 (DRB1*0401) and specific H2-A molecule in transgenic mice leads to collagen-induced arthritis. / Pan, Shuchong; Taneja, Veena D; Griffiths, Marie M.; Luthra, Harvinder; David, Chella S.

In: Human Immunology, Vol. 60, No. 9, 1999, p. 816-825.

Research output: Contribution to journalArticle

Pan, Shuchong ; Taneja, Veena D ; Griffiths, Marie M. ; Luthra, Harvinder ; David, Chella S. / Complementation between HLA-DR4 (DRB1*0401) and specific H2-A molecule in transgenic mice leads to collagen-induced arthritis. In: Human Immunology. 1999 ; Vol. 60, No. 9. pp. 816-825.
@article{970bc2406168483bb161ebe323fe079e,
title = "Complementation between HLA-DR4 (DRB1*0401) and specific H2-A molecule in transgenic mice leads to collagen-induced arthritis",
abstract = "We generated transgenic mice with DRB1*0401 gene with mutation in the β2 domain (aa 110 and 139) for better interaction with mCD4. The DR4 transgene was introduced into H2-A(q) (B10RQB3) and H2-A(f)(B10RFB3) to examine the role of DR4 in collagen arthritis. The HLA-DR molecules in these mice were found to be functional on the basis of their positive/negative selection of the Vβ T cell repertoire. H2-A(q) mice are resistant to porcine CII-induced arthritis. The RQB3/DR4 mice (H2A(q)/DR4) developed severe collagen induced arthritis (CIA) when immunized with Porcine type II collagen while the negative littermates were resistant. RQB3.DR4 mice were also highly susceptible to CIA induced by Human CII while negative littermates got only mild disease. However, RFB3/DR4 mice (H2A(f)/DR4) did not get CIA with any type II collagen. Therefore, the DR4 gene in the context of H2-A(q) predisposes to severe arthritis but not in the context of H2-Af. Antibodies to renatured cyanogen bromide (CB) cleaved fragments of PII in RQB3/DR4 mice and negative littermates suggest that the presence of DR4 does not result in any differences in specificity of antibody response to CB fragments. These results indicate that a specific gene complementation occurring between DR4 and H2.A(q) but not DR4 and H2A(f) promotes the induction of arthritis with PII and HII in these mice. A similar interaction may be involved between DR and DQ molecules in human RA.",
keywords = "In vivo model, MHC, Rheumatoid arthritis, Transgenic",
author = "Shuchong Pan and Taneja, {Veena D} and Griffiths, {Marie M.} and Harvinder Luthra and David, {Chella S.}",
year = "1999",
doi = "10.1016/S0198-8859(99)00070-1",
language = "English (US)",
volume = "60",
pages = "816--825",
journal = "Human Immunology",
issn = "0198-8859",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - Complementation between HLA-DR4 (DRB1*0401) and specific H2-A molecule in transgenic mice leads to collagen-induced arthritis

AU - Pan, Shuchong

AU - Taneja, Veena D

AU - Griffiths, Marie M.

AU - Luthra, Harvinder

AU - David, Chella S.

PY - 1999

Y1 - 1999

N2 - We generated transgenic mice with DRB1*0401 gene with mutation in the β2 domain (aa 110 and 139) for better interaction with mCD4. The DR4 transgene was introduced into H2-A(q) (B10RQB3) and H2-A(f)(B10RFB3) to examine the role of DR4 in collagen arthritis. The HLA-DR molecules in these mice were found to be functional on the basis of their positive/negative selection of the Vβ T cell repertoire. H2-A(q) mice are resistant to porcine CII-induced arthritis. The RQB3/DR4 mice (H2A(q)/DR4) developed severe collagen induced arthritis (CIA) when immunized with Porcine type II collagen while the negative littermates were resistant. RQB3.DR4 mice were also highly susceptible to CIA induced by Human CII while negative littermates got only mild disease. However, RFB3/DR4 mice (H2A(f)/DR4) did not get CIA with any type II collagen. Therefore, the DR4 gene in the context of H2-A(q) predisposes to severe arthritis but not in the context of H2-Af. Antibodies to renatured cyanogen bromide (CB) cleaved fragments of PII in RQB3/DR4 mice and negative littermates suggest that the presence of DR4 does not result in any differences in specificity of antibody response to CB fragments. These results indicate that a specific gene complementation occurring between DR4 and H2.A(q) but not DR4 and H2A(f) promotes the induction of arthritis with PII and HII in these mice. A similar interaction may be involved between DR and DQ molecules in human RA.

AB - We generated transgenic mice with DRB1*0401 gene with mutation in the β2 domain (aa 110 and 139) for better interaction with mCD4. The DR4 transgene was introduced into H2-A(q) (B10RQB3) and H2-A(f)(B10RFB3) to examine the role of DR4 in collagen arthritis. The HLA-DR molecules in these mice were found to be functional on the basis of their positive/negative selection of the Vβ T cell repertoire. H2-A(q) mice are resistant to porcine CII-induced arthritis. The RQB3/DR4 mice (H2A(q)/DR4) developed severe collagen induced arthritis (CIA) when immunized with Porcine type II collagen while the negative littermates were resistant. RQB3.DR4 mice were also highly susceptible to CIA induced by Human CII while negative littermates got only mild disease. However, RFB3/DR4 mice (H2A(f)/DR4) did not get CIA with any type II collagen. Therefore, the DR4 gene in the context of H2-A(q) predisposes to severe arthritis but not in the context of H2-Af. Antibodies to renatured cyanogen bromide (CB) cleaved fragments of PII in RQB3/DR4 mice and negative littermates suggest that the presence of DR4 does not result in any differences in specificity of antibody response to CB fragments. These results indicate that a specific gene complementation occurring between DR4 and H2.A(q) but not DR4 and H2A(f) promotes the induction of arthritis with PII and HII in these mice. A similar interaction may be involved between DR and DQ molecules in human RA.

KW - In vivo model

KW - MHC

KW - Rheumatoid arthritis

KW - Transgenic

UR - http://www.scopus.com/inward/record.url?scp=0032832918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032832918&partnerID=8YFLogxK

U2 - 10.1016/S0198-8859(99)00070-1

DO - 10.1016/S0198-8859(99)00070-1

M3 - Article

C2 - 10527388

AN - SCOPUS:0032832918

VL - 60

SP - 816

EP - 825

JO - Human Immunology

JF - Human Immunology

SN - 0198-8859

IS - 9

ER -