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

Miguel A. Gonzalez-Gay; Eric Zanelli; Christopher J. Krco; Gerald H. Nabozny; Julie Hanson; Marie M. Griffiths; Harvinder S. Luthra; Chella S. David

doi:10.1007/BF00164985

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

Miguel A. Gonzalez-Gay, Eric Zanelli, Christopher J. Krco, Gerald H. Nabozny, Julie Hanson, Marie M. Griffiths, Harvinder S. Luthra, Chella S. David

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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 Eβ^d molecule prevents CIA development in susceptible H2^q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F₁ mice, only H2Eb^d and H2Eb^s molecules showed protection. Using recombinant B10.RDD (Eb^d/b) mice, we found that CIA protection was mediated by the first domain of the Eβ^d molecule. Using peptides covering the third hypervariable region of the Eβ chain, we found a perfect correlation between presentation of Eβ peptides by the H2A^q molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of Eβ peptides for the H2A_q molecule.

Original language	English (US)
Pages (from-to)	35-40
Number of pages	6
Journal	Immunogenetics
Volume	42
Issue number	1
DOIs	https://doi.org/10.1007/BF00164985
State	Published - May 1995

ASJC Scopus subject areas

Immunology
Genetics

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title = "Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis",

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 Eβd 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 Eβd molecule. Using peptides covering the third hypervariable region of the Eβ chain, we found a perfect correlation between presentation of Eβ 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 Eβ peptides for the H2Aq molecule.",

author = "Gonzalez-Gay, {Miguel A.} and Eric Zanelli and Krco, {Christopher J.} and Nabozny, {Gerald H.} and Julie Hanson and Griffiths, {Marie M.} and Luthra, {Harvinder S.} and David, {Chella S.}",

year = "1995",

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doi = "10.1007/BF00164985",

language = "English (US)",

volume = "42",

pages = "35--40",

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T1 - Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis

AU - Gonzalez-Gay, Miguel A.

AU - Zanelli, Eric

AU - Krco, Christopher J.

AU - Nabozny, Gerald H.

AU - Hanson, Julie

AU - Griffiths, Marie M.

AU - Luthra, Harvinder S.

AU - David, Chella S.

PY - 1995/5

Y1 - 1995/5

N2 - 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 Eβd 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 Eβd molecule. Using peptides covering the third hypervariable region of the Eβ chain, we found a perfect correlation between presentation of Eβ 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 Eβ peptides for the H2Aq molecule.

AB - 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 Eβd 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 Eβd molecule. Using peptides covering the third hypervariable region of the Eβ chain, we found a perfect correlation between presentation of Eβ 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 Eβ peptides for the H2Aq molecule.

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

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