T cell immunity to type II collagen in the biobreeding rat

The identification and characterization of RT1u-restricted T cell epitopes on α1(II)

Michael A. Cremer, Xiu J. Ye, Linda Myers, David Brand, Edward F. Rosloniec, Andrew Kang

Research output: Contribution to journalArticle

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Abstract

Susceptibility to experimental collagen-induced arthritis in rodents is dependent on MHC class II elements to bind peptides from the type II collagen (CII) molecule. Although a substantial body of data has been reported in mice defining these peptide Ags, little has been reported in rats. In this study, we investigate the locations and sequences of CII peptides, which are bound by RT1u molecules, expressed by diabetic-resistant, arthritis- susceptible Biobreeding rats, and, in turn, stimulate CII-specific T cells. By using overlapping and substituted peptide homologues of CII, we have identified and characterized an immunodominant and five subdominant epitopes on CII, which stimulate RT1u-restricted T cell proliferation. The immunodominant epitope, CII (186-192), contains a QGPRG core sequence, which was found in a subdominant epitope CII (906-916). Similar sequences containing single conservative substitutions were identified in three other epitopes. One, CII (263-272), contained a conservatively substituted R→K substitution, whereas CII (880-889) and CII (906-916) contained nonconservative substitutions, i.e., P→D and R→M, respectively. Homologue peptides containing these sequences stimulated T cell proliferative responses, although less intensely than peptides containing CII (186-192). Substituting QGR residues in the QGPRG core with alanine, isoleucine, or proline reduced proliferation, as did substituting flanking E and G residues at the N terminus and E at the C terminus. Collectively, these data indicate that RT1u-restricted immunodominant and several subdominant epitopes on CII often share a QGPRG-like motif, with conservative substitutions present at either P or R positions. This motif is similar to one recognized by collagen-induced arthritis-susceptible HLA-DR1- and HLA-DR4-transgenic mice.

Original languageEnglish (US)
Pages (from-to)1795-1801
Number of pages7
JournalJournal of Immunology
Volume173
Issue number3
StatePublished - Aug 1 2004

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T-Lymphocyte Epitopes
Collagen Type II
Immunity
T-Lymphocytes
Peptides
Experimental Arthritis
Epitopes
HLA-DR1 Antigen
HLA-DR4 Antigen
Immunodominant Epitopes
Isoleucine
Proline
Alanine
Transgenic Mice
Arthritis
Rodentia
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

T cell immunity to type II collagen in the biobreeding rat : The identification and characterization of RT1u-restricted T cell epitopes on α1(II). / Cremer, Michael A.; Ye, Xiu J.; Myers, Linda; Brand, David; Rosloniec, Edward F.; Kang, Andrew.

In: Journal of Immunology, Vol. 173, No. 3, 01.08.2004, p. 1795-1801.

Research output: Contribution to journalArticle

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abstract = "Susceptibility to experimental collagen-induced arthritis in rodents is dependent on MHC class II elements to bind peptides from the type II collagen (CII) molecule. Although a substantial body of data has been reported in mice defining these peptide Ags, little has been reported in rats. In this study, we investigate the locations and sequences of CII peptides, which are bound by RT1u molecules, expressed by diabetic-resistant, arthritis- susceptible Biobreeding rats, and, in turn, stimulate CII-specific T cells. By using overlapping and substituted peptide homologues of CII, we have identified and characterized an immunodominant and five subdominant epitopes on CII, which stimulate RT1u-restricted T cell proliferation. The immunodominant epitope, CII (186-192), contains a QGPRG core sequence, which was found in a subdominant epitope CII (906-916). Similar sequences containing single conservative substitutions were identified in three other epitopes. One, CII (263-272), contained a conservatively substituted R→K substitution, whereas CII (880-889) and CII (906-916) contained nonconservative substitutions, i.e., P→D and R→M, respectively. Homologue peptides containing these sequences stimulated T cell proliferative responses, although less intensely than peptides containing CII (186-192). Substituting QGR residues in the QGPRG core with alanine, isoleucine, or proline reduced proliferation, as did substituting flanking E and G residues at the N terminus and E at the C terminus. Collectively, these data indicate that RT1u-restricted immunodominant and several subdominant epitopes on CII often share a QGPRG-like motif, with conservative substitutions present at either P or R positions. This motif is similar to one recognized by collagen-induced arthritis-susceptible HLA-DR1- and HLA-DR4-transgenic mice.",
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AU - Myers, Linda

AU - Brand, David

AU - Rosloniec, Edward F.

AU - Kang, Andrew

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AB - Susceptibility to experimental collagen-induced arthritis in rodents is dependent on MHC class II elements to bind peptides from the type II collagen (CII) molecule. Although a substantial body of data has been reported in mice defining these peptide Ags, little has been reported in rats. In this study, we investigate the locations and sequences of CII peptides, which are bound by RT1u molecules, expressed by diabetic-resistant, arthritis- susceptible Biobreeding rats, and, in turn, stimulate CII-specific T cells. By using overlapping and substituted peptide homologues of CII, we have identified and characterized an immunodominant and five subdominant epitopes on CII, which stimulate RT1u-restricted T cell proliferation. The immunodominant epitope, CII (186-192), contains a QGPRG core sequence, which was found in a subdominant epitope CII (906-916). Similar sequences containing single conservative substitutions were identified in three other epitopes. One, CII (263-272), contained a conservatively substituted R→K substitution, whereas CII (880-889) and CII (906-916) contained nonconservative substitutions, i.e., P→D and R→M, respectively. Homologue peptides containing these sequences stimulated T cell proliferative responses, although less intensely than peptides containing CII (186-192). Substituting QGR residues in the QGPRG core with alanine, isoleucine, or proline reduced proliferation, as did substituting flanking E and G residues at the N terminus and E at the C terminus. Collectively, these data indicate that RT1u-restricted immunodominant and several subdominant epitopes on CII often share a QGPRG-like motif, with conservative substitutions present at either P or R positions. This motif is similar to one recognized by collagen-induced arthritis-susceptible HLA-DR1- and HLA-DR4-transgenic mice.

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