Conserved T Cell Receptor Alpha-chain Induces Insulin Autoantibodies

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Jul 16

PMID 18626021

Citations 20

Authors

Masakazu Kobayashi

Jean Jasinski

Edwin Liu

Marcella Li

Dongmei Miao

Li Zhang

Liping Yu

Maki Nakayama

George S Eisenbarth

Affiliations

Soon will be listed here.

Abstract

A fundamental question is what are the molecular determinants that lead to spontaneous preferential targeting of specific autoantigens in autoimmune diseases, such as the insulin B:9-23 peptide sequence in type 1 diabetes. Anti-insulin B:9-23 T cell clones isolated from prediabetic NOD islets have a conserved Valpha-segment/Jalpha-segment, but no conservation of the alpha-chain N region and no conservation of the Vbeta-chain. Here, we show that the conserved T cell receptor alpha-chain generates insulin autoantibodies when transgenically or retrogenically introduced into mice without its corresponding Vbeta. We suggest that a major part of the mystery as to why islet autoimmunity develops relates to recognition of a primary insulin peptide by a conserved alpha chain T cell receptor.

Citing Articles

Using the T Cell Receptor as a Biomarker in Type 1 Diabetes.

Nakayama M, Michels A Front Immunol. 2021; 12:777788.

PMID: 34868047 PMC: 8635517. DOI: 10.3389/fimmu.2021.777788.

Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex.

Bettini M, Bettini M Front Endocrinol (Lausanne). 2018; 8:351.

PMID: 29312143 PMC: 5735072. DOI: 10.3389/fendo.2017.00351.

Molecular Interactions Governing Autoantigen Presentation in Type 1 Diabetes.

Nakayama M, Simmons K, Michels A Curr Diab Rep. 2015; 15(12):113.

PMID: 26458384 PMC: 4807868. DOI: 10.1007/s11892-015-0689-z.

Monoclonal antibody blocking the recognition of an insulin peptide-MHC complex modulates type 1 diabetes.

Zhang L, Crawford F, Yu L, Michels A, Nakayama M, Davidson H Proc Natl Acad Sci U S A. 2014; 111(7):2656-61.

PMID: 24550292 PMC: 3932899. DOI: 10.1073/pnas.1323436111.

Pathogenic CD4⁺ T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes.

Mohan J, Calderon B, Anderson M, Unanue E J Exp Med. 2013; 210(11):2403-14.

PMID: 24127484 PMC: 3804950. DOI: 10.1084/jem.20130582.

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