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Expression and function of mixed isotype MHC class II molecules in normal mice
J S Spencer1, J H Freed, R T Kubo
1Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Journal of Immunology (Baltimore, Md. : 1950)
|December 15, 1993
Summary
Despite extremely low surface expression, mixed isotype MHC class II molecules (Eαd Aβd) efficiently present peptides to T cells. This highlights their crucial role in T cell activation by low-level peptide-MHC complexes.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Mixed isotype MHC class II molecules (Eαd Aβd) are found at very low levels on normal mouse B cells and macrophages.
- Previous studies indicated that immunization with sperm whale myoglobin peptide 110-121 (SWM(110-121)) elicits T cells recognizing the peptide in the context of Eα Aβ.
Purpose of the Study:
- To characterize SWM(110-121)-specific T cell hybridomas from H-2d haplotype mice.
- To investigate the role of Eαd Aβd in peptide presentation despite its low expression.
Main Methods:
- Generation and characterization of SWM(110-121)-specific T cell hybridomas.
- Monoclonal antibody (mAb) inhibition experiments to assess MHC restriction.
- Surface staining with specific mAbs to determine MHC molecule levels.
Main Results:
- All Vβ8.2+ T cell hybridomas were restricted by Eαd Aβd.
- Half of Vβ8.2- hybridomas recognized the peptide via Eαd Aβd, while the others used I-Ad or I-Ed.
- Eαd Aβd demonstrated remarkable efficiency in presenting SWM(110-121) even at low peptide concentrations and low surface expression levels.
Conclusions:
- Eαd Aβd plays a significant role in T cell activation, particularly with low peptide antigen levels.
- The ability of antigen-presenting cells (APCs) to utilize Eαd Aβd despite low expression has critical implications for T cell immunity.