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Endogenous myelin basic protein inactivates the high avidity T cell repertoire
1Institute of Pathology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
The Journal of Experimental Medicine
|June 24, 1998
Summary
Endogenous myelin basic protein (MBP) is not required for selecting MBP-specific T cells. However, it causes T cells to become unresponsive to MBP, making key determinants appear cryptic.
Area of Science:
- Immunology
- Neuroscience
- T cell biology
Background:
- Myelin basic protein (MBP) is a key component of myelin.
- The T cell repertoire's selection is influenced by self-antigens.
Purpose of the Study:
- To investigate the role of endogenous MBP in the selection of MBP-specific T cells.
- To understand how MBP influences T cell responses and avidity.
Main Methods:
- Comparison of T cell responses to MBP in MBP-deficient (shiverer) and MBP-expressing (congenic C3H) mice.
- Immunization with MBP and MBP peptide (MBP:79-87) to assess T cell repertoire avidity.
Main Results:
- Shiverer mice developed a vigorous T cell response to MBP, recognizing both the protein and its peptide determinant (MBP:79-87).
- Congenic C3H mice showed unresponsiveness to MBP but responded to the peptide, indicating T cell inactivation by endogenous MBP.
- Endogenous MBP led to profound inactivation of high-avidity T cell clones specific for the immunodominant determinant.
Conclusions:
- Endogenous MBP is not essential for the positive selection of an MBP-specific T cell repertoire.
- Self-antigen exposure to MBP induces T cell unresponsiveness and makes specific determinants cryptic.