HLA class II influences the immune response and antibody diversification to Ro60/Sjögren's syndrome-A: Heightened antibody responses and epitope spreading in mice expressing HLA-DR molecules

Tawatchai Paisansinsup, Umesh S. Deshmukh, Vaidehi R. Chowdhary, Harvinder S. Luthra, Shu Man Fu, Chella S. David

Research output: Contribution to journalArticle

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Abstract

Abs to Ro/SSA Ags in the sera of patients with systemic lupus erythematosus and Sjögren's syndrome are influenced by the HLA class II genes. To investigate the role of individual HLA class II genes in immune responses to human Ro60 (hRo60), mice lacking murine class II molecules and carrying either HLA genes DR2(DRB1*1502), DR3(DRB1*0301), DQ6(DQA1*0103/DQB1*0601), or DQ8(DQA1*0301/DQB1*0302), were immunized with rhRo60. The results show that hRo60 induces strong T and B cell responses in DR2, DR3, and DQ8 mice in comparison to weaker responses in DQ6 mice. In all mice, the majority of the dominant T cell epitopes were located in the amino portion (aa 61-185) and the carboxy portion (aa 381-525) of the hRo60 molecules. In contrast, the early dominant B cell epitopes were located in the middle and carboxy portion of the hRo60 molecule (aa 281-315 and 401-538). In DR2, DR3, and DQ8 mice, the B cell epitopes subsequently spread to the amino and carboxy portion of the hRo60 molecule but were limited to the middle and carboxy portion in DQ6 mice. The DR2 and DR3 mice produced the highest titers of immunoprecipitating Abs against hRo60 and native mouse Ro60. In addition, only DR2 mice exclusively produced immunoprecipitating Abs to native mouse Ro52 and Abs to mouse La by slot blot analysis, whereas in other strains of mice Abs to mouse La were cross-reactive with the immunogen. The results of the present study demonstrate the importance of HLA class II in controlling the immune responses to the Ro-ribonucleoprotein.

Original languageEnglish (US)
Pages (from-to)5876-5884
Number of pages9
JournalJournal of Immunology
Volume168
Issue number11
StatePublished - Jun 1 2002

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HLA-DR Antigens
Antibody Formation
Epitopes
B-Lymphocyte Epitopes
MHC Class II Genes
HLA-DR2 Antigen
T-Lymphocyte Epitopes
Systemic Lupus Erythematosus
B-Lymphocytes

ASJC Scopus subject areas

  • Immunology

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HLA class II influences the immune response and antibody diversification to Ro60/Sjögren's syndrome-A : Heightened antibody responses and epitope spreading in mice expressing HLA-DR molecules. / Paisansinsup, Tawatchai; Deshmukh, Umesh S.; Chowdhary, Vaidehi R.; Luthra, Harvinder S.; Fu, Shu Man; David, Chella S.

In: Journal of Immunology, Vol. 168, No. 11, 01.06.2002, p. 5876-5884.

Research output: Contribution to journalArticle

Paisansinsup, Tawatchai ; Deshmukh, Umesh S. ; Chowdhary, Vaidehi R. ; Luthra, Harvinder S. ; Fu, Shu Man ; David, Chella S. / HLA class II influences the immune response and antibody diversification to Ro60/Sjögren's syndrome-A : Heightened antibody responses and epitope spreading in mice expressing HLA-DR molecules. In: Journal of Immunology. 2002 ; Vol. 168, No. 11. pp. 5876-5884.
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abstract = "Abs to Ro/SSA Ags in the sera of patients with systemic lupus erythematosus and Sj{\"o}gren's syndrome are influenced by the HLA class II genes. To investigate the role of individual HLA class II genes in immune responses to human Ro60 (hRo60), mice lacking murine class II molecules and carrying either HLA genes DR2(DRB1*1502), DR3(DRB1*0301), DQ6(DQA1*0103/DQB1*0601), or DQ8(DQA1*0301/DQB1*0302), were immunized with rhRo60. The results show that hRo60 induces strong T and B cell responses in DR2, DR3, and DQ8 mice in comparison to weaker responses in DQ6 mice. In all mice, the majority of the dominant T cell epitopes were located in the amino portion (aa 61-185) and the carboxy portion (aa 381-525) of the hRo60 molecules. In contrast, the early dominant B cell epitopes were located in the middle and carboxy portion of the hRo60 molecule (aa 281-315 and 401-538). In DR2, DR3, and DQ8 mice, the B cell epitopes subsequently spread to the amino and carboxy portion of the hRo60 molecule but were limited to the middle and carboxy portion in DQ6 mice. The DR2 and DR3 mice produced the highest titers of immunoprecipitating Abs against hRo60 and native mouse Ro60. In addition, only DR2 mice exclusively produced immunoprecipitating Abs to native mouse Ro52 and Abs to mouse La by slot blot analysis, whereas in other strains of mice Abs to mouse La were cross-reactive with the immunogen. The results of the present study demonstrate the importance of HLA class II in controlling the immune responses to the Ro-ribonucleoprotein.",
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AU - Deshmukh, Umesh S.

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AU - Luthra, Harvinder S.

AU - Fu, Shu Man

AU - David, Chella S.

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