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Recognition of measles virus-infected cells by CD8+ T cells depends on the H-2 molecule
1Institute of Virology and Immunobiology, University of Würzburg, Germany.
Abstract:
H-2d mice are resistant to measles virus-induced encephalitis (MVE) and develop Ld-restricted CD8+ T cells which lyse target cells infected with measles virus or with a vaccinia virus recombinant expressing the nucleocapsid protein of measles virus (vvN). In contrast, H-2k mice are susceptible to MVE and generate CD8+ T cells which lyse target cells infected with vvN, but not those infected with MV. We were able to demonstrate that this difference is not due to a defect in the antigen processing machinery, but that Kk molecules require 100-fold more peptide to sensitize target cells for lysis by CTL. vvN replicates well in target cells and therefore enhances the level of epitope peptide available for CTL recognition. In contrast, MV infection is abortive in mouse cells and low levels of epitope peptide are produced. As Ld requires 100-fold less peptide than Kk to sensitize target cells for lysis, the low level of epitope peptide is enough to induce lysis by CD8+ T cells, whereas for recognition via Kk, increased synthesis of protein is required. We propose that the differences in peptide binding between the two H-2 molecules will have consequences for the kinetics of the generation of CD8+ T cells as well as the absolute numbers of CD8+ T cells generated.
Insights
Mice resistant to measles virus encephalitis (MVE) generate effective CD8+ T cells. Susceptible mice require higher peptide levels for T cell activation, impacting immune response generation.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Measles virus-induced encephalitis (MVE) susceptibility varies between mouse strains.
- H-2d mice are resistant, developing Ld-restricted CD8+ T cells, while H-2k mice are susceptible.
Purpose of the Study:
- To investigate the molecular basis for differential CD8+ T cell responses in H-2d versus H-2k mice against measles virus.
- To determine the role of antigen processing and peptide presentation in MVE pathogenesis.
Main Methods:
- Utilized H-2d and H-2k mice models.
- Employed measles virus (MV) and vaccinia virus recombinant (vvN) infection models.
- Assessed cytotoxic T lymphocyte (CTL) lysis of infected target cells.
Main Results:
- H-2k molecules require 100-fold more peptide than H-2d molecules to sensitize target cells for CTL lysis.
- Abortive MV infection in mouse cells leads to low epitope peptide levels, insufficient for H-2k recognition.
- Efficient vvN replication enhances epitope peptide availability, enabling H-2k mediated lysis.
Conclusions:
- Differential peptide binding affinities of H-2d (Ld) and H-2k molecules significantly influence CD8+ T cell responses to MV.
- Peptide presentation efficiency, rather than antigen processing defects, explains the observed differences in MVE resistance.
- H-2 molecule peptide-binding characteristics impact T cell kinetics and generation, affecting viral encephalitis outcomes.