Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 20 December 1991:
Vol. 254. no. 5039, pp. 1756 - 1761
DOI: 10.1126/science.1763324
Prev | Table of Contents | Next

Articles

Science, Vol 254, Issue 5039, 1756-1761
Copyright © 1991 by American Association for the Advancement of Science

articles

Linkage of faulty major histocompatibility complex class I to autoimmune diabetes

D Faustman, XP Li, HY Lin, YE Fu, G Eisenbarth, J Avruch, and J Guo

Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Charlestown 02129.

Pancreatic islet cells are the targets of an autoimmune response in type I diabetes. In the nonobese diabetic (NOD) mouse model of autoimmune diabetes, expression of major histocompatibility complex (MHC) class I proteins was inversely correlated with diabetes; in this mouse a mutation in the MHC class II-linked gene for the putative MHC class I peptide transporter was also present. Mice deficient in MHC class I expression because they do not produce beta 2-microglobulin also developed late onset autoimmune diabetes. In cells from humans with type I diabetes expression of MHC class I was decreased; subsets of prediabetics categorized as most likely to become hyperglycemic also had low MHC class I. T cell responses to self antigens are faulty in diabetics. In sets of genetically identical twins that are discordant for diabetes, the defect appeared to reside with the antigen presenting cell. Thus, a lack of surface MHC class I protein is associated with autoimmune diabetes; the concomitant defect in antigen presentation may impair the development of self tolerance, which could result in autoimmune disease.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Immunotherapy on Trial for New-Onset Type 1 Diabetes.
D. L. Faustman (2008)
N. Engl. J. Med. 359, 1956-1958
   Full Text »    PDF »
Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism.
L. Ban, J. Zhang, L. Wang, W. Kuhtreiber, D. Burger, and D. L. Faustman (2008)
PNAS 105, 13644-13649
   Abstract »    Full Text »    PDF »
Reversal of Sjogren's-like syndrome in non-obese diabetic mice.
S. D Tran, S. Kodama, B. M Lodde, I. Szalayova, S. Key, S. Khalili, D. L Faustman, and E. Mezey (2007)
Ann Rheum Dis 66, 812-814
   Abstract »    Full Text »    PDF »
Prediction of HLA-DQ3.2{beta} Ligands: evidence of multiple registers in class II binding peptides.
J. C. Tong, G. L. Zhang, T. W. Tan, J. T. August, V. Brusic, and S. Ranganathan (2006)
Bioinformatics 22, 1232-1238
   Abstract »    Full Text »    PDF »
Major Histocompatibility Complex Class I Shedding and Programmed Cell Death Stimulated Through the Proinflammatory P2X7 Receptor: A Candidate Susceptibility Gene for NOD Diabetes.
J. I. Elliott and C. F. Higgins (2004)
Diabetes 53, 2012-2017
   Abstract »    Full Text »    PDF »
Islet Regeneration During the Reversal of Autoimmune Diabetes in NOD Mice.
S. Kodama, W. Kuhtreiber, S. Fujimura, E. A. Dale, and D. L. Faustman (2003)
Science 302, 1223-1227
   Abstract »    Full Text »    PDF »
Role of Defective Apoptosis in Type 1 Diabetes and Other Autoimmune Diseases.
T. Hayashi and D. L. Faustman (2003)
Recent Prog. Horm. Res. 58, 131-153
   Abstract »    Full Text »    PDF »
Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Association of gender-related LMP2 inactivation with autoimmune pathogenesis.
T. Hayashi and D. L. Faustman (2001)
J Appl Physiol 91, 2804-2815
   Abstract »    Full Text »    PDF »
Homotypic cluster formation of dendritic cells, a close correlate of their state of maturation. Defects in the biobreeding diabetes-prone rat.
F. G. A. Delemarre, P. G. Hoogeveen, M. de Haan-Meulman, P. J. Simons, and H. A. Drexhage (2001)
J. Leukoc. Biol. 69, 373-380
   Abstract »    Full Text »
NOD Mice Are Defective in Proteasome Production and Activation of NF-kappa B.
T. Hayashi and D. Faustman (1999)
Mol. Cell. Biol. 19, 8646-8659
   Abstract »    Full Text »    PDF »
Signs of Immaturity of Splenic Dendritic Cells from the Autoimmune Prone Biobreeding Rat: Consequences for the In Vitro Expansion of Regulator and Effector T Cells.
F. G. A. Delemarre, P. J. Simons, H. J. de Heer, and H. A. Drexhage (1999)
J. Immunol. 162, 1795-1801
   Abstract »    Full Text »    PDF »
Novel Splicing of the Human MHC-Encoded Peptide Transporter Confers Unique Properties.
G. Yan, L. Shi, and D. Faustman (1999)
J. Immunol. 162, 852-859
   Abstract »    Full Text »    PDF »
Subcongenic Analysis of the Idd13 Locus in NOD/Lt Mice: Evidence for Several Susceptibility Genes Including a Possible Diabetogenic Role for {beta}2-Microglobulin.
D. V. Serreze, M. Bridgett, H. D. Chapman, E. Chen, S. D. Richard, and E. H. Leiter (1998)
J. Immunol. 160, 1472-1478
   Abstract »    Full Text »    PDF »
Benzene--a Review of the Literature from a Health Effects Perspective.
G. L. Gist and J. R. Burg (1997)
Toxicology and Industrial Health 13, 661-714
   Abstract »    PDF »
The Pathogenesis of Insulin-Dependent Diabetes Mellitus.
M. A. Atkinson and N. K. Maclaren (1994)
N. Engl. J. Med. 331, 1428-1436
   Full Text »
The Genetics of Autoimmune Diabetes: Approaching a Solution to the Problem.
W. E. Winter, T. Chihara, and D. Schatz (1993)
Arch Pediatr Adolesc Med 147, 1282-1290
   Abstract »    PDF »
New Directions in the Immunology of Autoimmune Diabetes.
K. C. Herold and A. H. Rubenstein (1992)
Ann Intern Med 117, 436-438
   Abstract »    PDF »
Expression of intra-MHC transporter (Ham) genes and class I antigens in diabetes-susceptible NOD mice.
H. Gaskins, J. Monaco, and E. Leiter (1992)
Science 256, 1826-1828
   PDF »
Expression of intra-MHC transporter (Ham) genes and class I antigens in diabetes-susceptible NOD mice.
L. Wicker, P. Podolin, P Fischer, A Sirotina, R. Boltz Jr, and L. Peterson (1992)
Science 256, 1828-1830
   PDF »
Response.
D. Faustman, X. Li, H. Y. Lin, R. Huang, and J. Guo (1992)
Science 256, 1830-1831
   PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)