Home LiteratureArticle Details

PMID: 7797266 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis.

Immunogenetics ·Vol. 42 ·No. 1 ·1995-00-00 ·Pages 35-40

Gonzalez-Gay MA, Zanelli E, Krco CJ, Nabozny GH, Hanson J, Griffiths MM, Luthra HS, David CS

Abstract

Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E beta d molecule prevents CIA development in susceptible H2q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F1 mice, only H2Ebd and H2Ebs molecules showed protection. Using recombinant B10.RDD (Ebd/b) mice, we found that CIA protection was mediated by the first domain of the E beta d molecule. Using peptides covering the third hypervariable region of the E beta chain, we found a perfect correlation between presentation of E beta peptides by the H2Aq molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2Aq molecule.

MeSH Terms

Amino Acid Sequence Animals Arthritis/immunology Collagen/immunology Genes, MHC Class II H-2 Antigens/genetics HLA-DQ Antigens/genetics HLA-DR Antigens/genetics HLA-DRB1 Chains Mice Mice, Inbred DBA Molecular Sequence Data Polymorphism, Genetic

Chemicals

H-2 Antigens HLA-DQ Antigens HLA-DR Antigens HLA-DRB1 Chains Collagen

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Gonzalez-Gay M A

Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.

Zanelli E

Krco C J

Nabozny G H

Hanson J

Griffiths M M

Luthra H S

David C S

References (35)

35 references, click to expand

Determination of tolerance to self E alpha peptides by clonal elimination of H-2E reactive T cells and antigen presentation by H-2A molecules.
Transplantation. 1992 Nov;54(5):920-3 PMID: 1440860
Localization of a critical restriction site on the I-A beta chain that determines susceptibility to collagen-induced arthritis in mice.
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9475-9 PMID: 2512582
Tolerance to a self-peptide from the third hypervariable region of HLA DRB1*0401 in rheumatoid arthritis patients and normal subjects.
J Immunol. 1994 Dec 1;153(11):5321-9 PMID: 7963584
Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified I-A beta-chain or normal I-E alpha-chain.
Nature. 1990 Jun 21;345(6277):727-9 PMID: 2163026
Monoclonal antibody against an Ir gene product?
J Exp Med. 1980 Oct 1;152(4):1085-101 PMID: 6158546
Molecular analysis and repair of a defective Ef alpha gene.
J Immunol. 1989 Jun 1;142(11):4034-40 PMID: 2497187
Protective role of major histocompatibility complex class II Ebd transgene on collagen-induced arthritis.
J Exp Med. 1994 Oct 1;180(4):1559-64 PMID: 7931088
Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens.
J Immunol. 1980 Feb;124(2):533-40 PMID: 7188699
Population genetics of rheumatoid arthritis.
Rheum Dis Clin North Am. 1992 Nov;18(4):741-59 PMID: 1280845
Prevention of systemic lupus erythematosus in autoimmune BXSB mice by a transgene encoding I-E alpha chain.
J Exp Med. 1993 Oct 1;178(4):1189-97 PMID: 8376928
Prevention of autoimmune insulitis by expression of I-E molecules in NOD mice.
Nature. 1987 Jul 30-Aug 5;328(6129):432-4 PMID: 3302721
Monoclonal antibodies to mouse major histocompatibility complex antigens.
Transplantation. 1982 Sep;34(3):113-20 PMID: 7135466
Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates.
J Exp Med. 1981 Sep 1;154(3):688-700 PMID: 6792316
Molecular analysis of the hotspot of recombination in the murine major histocompatibility complex.
Science. 1986 Oct 10;234(4773):173-9 PMID: 3018929
Several mechanisms can account for defective E alpha gene expression in different mouse haplotypes.
Proc Natl Acad Sci U S A. 1983 Jan;80(1):273-7 PMID: 6296871
The genetic basis of rheumatoid arthritis. The shared epitope hypothesis.
Rheum Dis Clin North Am. 1992 Nov;18(4):761-83 PMID: 1280846
Characterization of the molecular defects in the mouse E beta f and E beta q genes. Implications for the origin of MHC polymorphism.
J Immunol. 1990 Mar 1;144(5):1957-64 PMID: 2106558
Structures on the I-A molecule predisposing for susceptibility to type II collagen-induced autoimmune arthritis.
Eur J Immunol. 1990 Sep;20(9):2127-31 PMID: 2209706
Structural model for T-cell recognition of HLA class II-associated alloepitopes.
Hum Immunol. 1990 Jan;27(1):51-72 PMID: 1689285
H-2-linked control of the Yaa gene-induced acceleration of lupus-like autoimmune disease in BXSB mice.
Eur J Immunol. 1992 Feb;22(2):295-9 PMID: 1537372
Homozygosity for the HLA-DRB1 allele selects for extraarticular manifestations in rheumatoid arthritis.
J Clin Invest. 1992 Jun;89(6):2033-9 PMID: 1602009
Genes of the major histocompatibility complex of the mouse.
Annu Rev Immunol. 1983;1:529-68 PMID: 6152713
I-E+ nonobese diabetic mice develop insulitis and diabetes.
J Exp Med. 1993 Sep 1;178(3):793-803 PMID: 8350054
MHC class-II molecules and autoimmunity.
Annu Rev Immunol. 1991;9:493-525 PMID: 1910687
Collagen arthritis as a relevant model for rheumatoid arthritis.
Arthritis Rheum. 1982 Aug;25(8):911-6 PMID: 7052093
Variable synthesis and expression of E alpha and Ae (E beta) Ia polypeptide chains in mice of different H-2 haplotypes.
Immunogenetics. 1981;12(3-4):321-37 PMID: 6937437
The MHC molecule I-E is necessary but not sufficient for the clonal deletion of V beta 11-bearing T cells.
J Exp Med. 1989 Apr 1;169(4):1405-19 PMID: 2538552
Requirement for cotolerogenic gene products in the clonal deletion of I-E reactive T cells.
Science. 1990 Feb 23;247(4945):964-7 PMID: 1968289
Expression of a transgenic class II Ab gene confers susceptibility to collagen-induced arthritis.
Eur J Immunol. 1994 Jul;24(7):1698-702 PMID: 8026530
Tolerance to a self peptide from the third hypervariable region of the Es beta chain. Implications for molecular mimicry models of autoimmune disease.
Eur J Immunol. 1991 Sep;21(9):2063-7 PMID: 1889457
The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis.
Arthritis Rheum. 1987 Nov;30(11):1205-13 PMID: 2446635
The E-linked subregion of the major histocompatibility complex down-regulates autoimmunity in NZB x NZW F1 mice.
Immunogenetics. 1994;40(2):150-3 PMID: 8026863
Development of autoimmune insulitis is prevented in E alpha d but not in A beta k NOD transgenic mice.
Int Immunol. 1989;1(2):209-13 PMID: 2562156
Type II collagen-induced arthritis in mice. IV. Variations in immunogenetic regulation provide evidence for multiple arthritogenic epitopes on the collagen molecule.
J Immunol. 1985 Oct;135(4):2443-51 PMID: 2411796
Evolutionary relationships between the t and H-2 haplotypes in the house mouse.
Immunogenetics. 1984;19(4):311-20 PMID: 6201441

Article Info

Journal

Immunogenetics

Abbr.

Immunogenetics

ISSN

0093-7711

DOI

10.1007/BF00164985

Published

1995-00-00

Pages

35-40

Language

English

Region

United States

NLM ID

0420404

Subset

Grants

NIAMS NIH HHS · AR 30752 · United States

NCI NIH HHS · CA 09127 · United States

External Links

PubMed source DOI: 10.1007/BF00164985 View journal details

Analysis Services

Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis.

Contact

WeChat Official Account