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A shared TCR CDR3 sequence in NOD mouse autoimmune diabetes.
Y Tikochinski1, D Elias, C Steeg
1The Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
International Immunology
|June 9, 1999
Summary
A specific T cell receptor (TCR) beta chain sequence is common in NOD mice with autoimmune diabetes. This sequence is linked to the heat shock protein 60 (hsp60) and appears early in T cells, suggesting its role in disease development.
Area of Science:
- Immunology
- Autoimmunity
- T cell receptor (TCR) research
Background:
- T cell receptors (TCRs) are crucial in autoimmune diseases, with their genetic makeup influencing disease pathology.
- The NOD mouse model is frequently used to study Type 1 diabetes, an autoimmune condition.
Purpose of the Study:
- To characterize the TCR alpha and beta chains of the CD4(+) T cell clone C9, which plays a role in NOD mouse diabetes.
- To investigate the T cell receptor (TCR) CDR3 beta chain sequence prevalence in NOD mice and its association with autoimmune diabetes.
Main Methods:
- Sequencing of the alpha and beta chains of the TCR from the C9 T cell clone.
- Analysis of the CDR3 peptide sequence of the TCR beta chain.
- Detection of the CDR3 element in thymus, spleen, and autoimmune insulitis in NOD mice at different ages.
Main Results:
- The C9 T cell clone recognizes a peptide epitope (p277) from the 60 kDa heat shock protein (hsp60).
- A specific CDR3 peptide sequence in the C9 TCR beta chain is prevalent among NOD mice.
- This prevalent TCR CDR3beta sequence is detectable early in the thymus (2 weeks) and later in the spleen and insulitis, indicating its association with autoimmune diabetes.
Conclusions:
- The identified TCR CDR3beta sequence is a common idiotope associated with autoimmune diabetes in NOD mice.
- This finding provides insights into the T cell receptor repertoire involved in autoimmune diabetes and suggests potential diagnostic or therapeutic targets.