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The alloreactive T cell response against the class Ib molecule H2-M3 is specific for high affinity peptides
V M Dabhi1, R Hovik, L Van Kaer
1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|November 20, 1998
Summary
Mitochondrial peptides presented by MHC class Ib molecule H2-M3 to CD8+ cytotoxic T lymphocytes (CTLs) vary in binding affinity. High-affinity peptides elicit strong CTL responses, demonstrating peptide specificity in alloantigenicity.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- MHC class Ib molecule H2-M3 presents N-formylated peptides to CD8+ cytotoxic T lymphocytes (CTLs).
- Endogenous N-formylated peptides can originate from mitochondrial genome-encoded proteins.
Purpose of the Study:
- To investigate the binding affinities of mitochondrial peptides to H2-M3.
- To determine the correlation between peptide binding affinity and CTL alloreactivity.
Main Methods:
- Peptide competition assays were used to assess binding affinities of 13 mitochondrial peptides to H2-M3.
- Mixed lymphocyte cultures and long-term CTL lines/clones were used to evaluate CTL responses.
Main Results:
- Two mitochondrial peptides exhibited high affinity for H2-M3, six showed intermediate affinity, three had low affinity, and two did not bind.
- Alloreactive CTLs responded strongly to high-affinity peptides and occasionally to intermediate-affinity peptides.
- Established CTL lines and clones reacted exclusively with high-affinity peptides.
Conclusions:
- Alloreactive CTL responses are dependent on specific peptide binding to MHC class I molecules.
- Peptide affinity for H2-M3 directly correlates with the alloantigenicity of the presented peptide.