Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes- associated human MHC class II allele, DRB1*0401

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Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes- associated human MHC class II allele, DRB1*0401. / Wicker, Linda S.; Chen, Shiow Ling; Nepom, Gerald T.; Elliott, John F.; Freed, Daniel C.; Bansal, Alka; Zheng, Song; Herman, Andrew; Lernmark, Åke; Zaller, Dennis M.; Peterson, Laurence B.; Rothbard, Jonathan B.; Cummings, Richard; Whiteley, Phyllis J.

In: Journal of Clinical Investigation, Vol. 98, No. 11, 01.12.1996, p. 2597-2603.

Research output: Contribution to journalArticle

Harvard

Wicker, LS, Chen, SL, Nepom, GT, Elliott, JF, Freed, DC, Bansal, A, Zheng, S, Herman, A, Lernmark, Å, Zaller, DM, Peterson, LB, Rothbard, JB, Cummings, R & Whiteley, PJ 1996, 'Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes- associated human MHC class II allele, DRB1*0401', Journal of Clinical Investigation, vol. 98, no. 11, pp. 2597-2603. https://doi.org/10.1172/JCI119079

APA

Wicker, L. S., Chen, S. L., Nepom, G. T., Elliott, J. F., Freed, D. C., Bansal, A., Zheng, S., Herman, A., Lernmark, Å., Zaller, D. M., Peterson, L. B., Rothbard, J. B., Cummings, R., & Whiteley, P. J. (1996). Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes- associated human MHC class II allele, DRB1*0401. Journal of Clinical Investigation, 98(11), 2597-2603. https://doi.org/10.1172/JCI119079

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Author

Wicker, Linda S. ; Chen, Shiow Ling ; Nepom, Gerald T. ; Elliott, John F. ; Freed, Daniel C. ; Bansal, Alka ; Zheng, Song ; Herman, Andrew ; Lernmark, Åke ; Zaller, Dennis M. ; Peterson, Laurence B. ; Rothbard, Jonathan B. ; Cummings, Richard ; Whiteley, Phyllis J. / Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes- associated human MHC class II allele, DRB1*0401. In: Journal of Clinical Investigation. 1996 ; Vol. 98, No. 11. pp. 2597-2603.

RIS

TY - JOUR

T1 - Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes- associated human MHC class II allele, DRB1*0401

AU - Wicker, Linda S.

AU - Chen, Shiow Ling

AU - Nepom, Gerald T.

AU - Elliott, John F.

AU - Freed, Daniel C.

AU - Bansal, Alka

AU - Zheng, Song

AU - Herman, Andrew

AU - Lernmark, Åke

AU - Zaller, Dennis M.

AU - Peterson, Laurence B.

AU - Rothbard, Jonathan B.

AU - Cummings, Richard

AU - Whiteley, Phyllis J.

PY - 1996/12/1

Y1 - 1996/12/1

N2 - The identification of class II binding peptide epitopes from autoimmune disease-related antigens is an essential step in the development of antigen- specific immune modulation therapy. In the case of type 1 diabetes, T cell and B cell reactivity to the autoantigen glutamic acid decarboxylase 65 (GAD65) is associated with disease development in humans and in nonobese diabetic (NOD) mice. In this study, we identify two DRB1*0401-restricted T cell epitopes from human GAD65, 274-286, and 115-127. Both peptides are immunogenic in transgenic mice expressing functional DRB1*0401 MHC class II molecules but not in nontransgenic littermates. Processing of GAD65 by antigen presenting cells (APC) resulted in the formation of DRB1*0401 complexes loaded with either the 274-286 or 115-127 epitopes, suggesting that these naturally derived epitopes may be displayed on APC recruited into pancreatic islets. The presentation of these two T cell epitopes in the islets of DRB1*0401 individuals who are at risk for type 1 diabetes may allow for antigen-specific recruitment of regulatory cells to the islets following peptide immunization.

AB - The identification of class II binding peptide epitopes from autoimmune disease-related antigens is an essential step in the development of antigen- specific immune modulation therapy. In the case of type 1 diabetes, T cell and B cell reactivity to the autoantigen glutamic acid decarboxylase 65 (GAD65) is associated with disease development in humans and in nonobese diabetic (NOD) mice. In this study, we identify two DRB1*0401-restricted T cell epitopes from human GAD65, 274-286, and 115-127. Both peptides are immunogenic in transgenic mice expressing functional DRB1*0401 MHC class II molecules but not in nontransgenic littermates. Processing of GAD65 by antigen presenting cells (APC) resulted in the formation of DRB1*0401 complexes loaded with either the 274-286 or 115-127 epitopes, suggesting that these naturally derived epitopes may be displayed on APC recruited into pancreatic islets. The presentation of these two T cell epitopes in the islets of DRB1*0401 individuals who are at risk for type 1 diabetes may allow for antigen-specific recruitment of regulatory cells to the islets following peptide immunization.

KW - autoimmunity

KW - diabetes mellitus, insulin-dependent

KW - MHC class II

KW - mice, inbred NOD

KW - peptide autoantigens

U2 - 10.1172/JCI119079

DO - 10.1172/JCI119079

M3 - Article

C2 - 8958223

AN - SCOPUS:10544223741

VL - 98

SP - 2597

EP - 2603

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 11

ER -