A Cartilage-Mimicking T-Cell Epitope on a 65K Mycobacterial Heat-Shock Protein: Adjuvant Arthritis as a Model for Human Rheumatoid Arthritis

Eden, Willem van; Hogervorst, E. J. M.; Hensen, E. J.; Zee, Ruurd van der; Embden, J. D. A. Van; Cohen, Irun R.

doi:10.1007/978-3-642-74594-2_3

Cited by 59 publications

(34 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results demonstrate that the T cell repertoire potentially reactive against cryptic determinants within a foreign Ag (Bhsp65) could be engaged and primed by the corresponding dominant determinants of the self homolog (Rhsp65). Molecular mimicry between microbial and host Ags has been proposed as a mechanism for the initiation of autoimmunity in several animal models as well as in humans (31)(32)(33)(34)(35). In contrast, our results suggest that cross-reactivity between homologous foreign and self hsp65 plays a role in diversification of T cell response to disease-regulating epitopes of foreign hsp65 during the course of AA, and in regulation of autoimmune arthritis.…”

Section: Discussioncontrasting

confidence: 50%

The Regulatory C-Terminal Determinants within Mycobacterial Heat Shock Protein 65 Are Cryptic and Cross-Reactive with the Dominant Self Homologs: Implications for the Pathogenesis of Autoimmune Arthritis

Durai

Kim

Moudgil

2004

The Journal of Immunology

View full text Add to dashboard Cite

The 65-kDa mycobacterial heat shock protein (Bhsp65) has been invoked in the pathogenesis of both adjuvant arthritis (AA) in the Lewis rat (RT.1l) and human rheumatoid arthritis. Arthritic Lewis rats in the late phase of AA show diversification of the T cell response to Bhsp65 C-terminal determinants (BCTD), and pretreatment of naive Lewis rats with a mixture of peptides representing these neoepitopes affords protection against AA. However, the fine specificity and physiologic significance of the BCTD-directed T cell repertoire, and the role of homologous self (rat) hsp65 (Rhsp65), if any, in spreading of the T cell response to Bhsp65 have not yet been examined. We observed that T cells primed by peptides comprising BCTD can adoptively transfer protection against AA to the recipient Lewis rats. However, these T cells can be activated by preprocessed (peptide) form of BCTD, but not native Bhsp65, showing that BCTD are cryptic epitopes. The BCTD-reactive T cells can be activated by the naturally generated (dominant) C-terminal epitopes of both exogenous and endogenous Rhsp65 and vice versa. Furthermore, certain individual peptides constituting BCTD and their self homologs can also induce protection against AA. These results support a model for the diversification of T cell response to Bhsp65 during the course of AA involving up-regulation of the display of cryptic BCTD coupled with spontaneous induction of T cell response to the cross-reactive dominant C-terminal epitopes of Rhsp65. The identification of disease-regulating cryptic determinants in Ags implicated in arthritis provides a novel approach for immunotherapy of rheumatoid arthritis.

show abstract

Section: Discussioncontrasting

confidence: 50%

The Regulatory C-Terminal Determinants within Mycobacterial Heat Shock Protein 65 Are Cryptic and Cross-Reactive with the Dominant Self Homologs: Implications for the Pathogenesis of Autoimmune Arthritis

Durai

Kim

Moudgil

2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The strong association of disease onset with T-cell response to bacterial Hsp65 and to human Hsp60, in animal models of experimental adjuvant arthritis (AA) and of diabetes in NOD mice, respectively, together with the capacity of Hsp-reactive T-cell lines and clones to transfer disease to naive animals, support the proinflammatory function of the Hsp-reactive T-cell repertoire [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

T-Cell autoreactivity to Hsp in human transplantation may involve both proinflammatory and regulatory functions

et al. 2004

View full text Add to dashboard Cite

“…As one of the mechanisms for activation of autoaggressive T cells has been suggested to be based on crossreactivity with infectious agents [9][10][11][12][13], we wanted to address the clonality of the autoreactive T cell response in an autoimmune model not induced by the auto-antigen itself. We therefore used Adjuvant Arthritis (AA), which is induced by injection of Mycobacterium tuberculosis (Mt) in incomplete Freunds adjuvant (IFA).…”

Section: Introductionmentioning

confidence: 99%

Generation and Characterization of a Clonotypic Antibody Specific for the T Cell Receptor of an Arthritogenic T Cell Clone—Studies in Adjuvant Arthritis

Tienhoven

Steenbakkers²,

Veenstra

et al. 2000

Journal of Autoimmunity

View full text Add to dashboard Cite

A Cartilage-Mimicking T-Cell Epitope on a 65K Mycobacterial Heat-Shock Protein: Adjuvant Arthritis as a Model for Human Rheumatoid Arthritis

Cited by 59 publications

References 41 publications

The Regulatory C-Terminal Determinants within Mycobacterial Heat Shock Protein 65 Are Cryptic and Cross-Reactive with the Dominant Self Homologs: Implications for the Pathogenesis of Autoimmune Arthritis

The Regulatory C-Terminal Determinants within Mycobacterial Heat Shock Protein 65 Are Cryptic and Cross-Reactive with the Dominant Self Homologs: Implications for the Pathogenesis of Autoimmune Arthritis

T-Cell autoreactivity to Hsp in human transplantation may involve both proinflammatory and regulatory functions

Generation and Characterization of a Clonotypic Antibody Specific for the T Cell Receptor of an Arthritogenic T Cell Clone—Studies in Adjuvant Arthritis

Contact Info

Product

Resources

About