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Cytolytic T cells activated by H-2-controlled E molecules cross-react with A molecules
Immunogenetics
|January 1, 1982
Summary
Cytolytic T lymphocytes stimulated by E molecules can recognize cells lacking E molecules but expressing A molecules. This E-A cross-reactivity suggests a shared evolutionary origin for A- and E-encoding loci.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Cell-mediated lymphocytotoxicity involves T lymphocytes recognizing foreign antigens on cell surfaces.
- The H-2 complex in mice encodes major histocompatibility complex (MHC) molecules, including class I (K) and class II (E, A) molecules, crucial for immune responses.
- Differences in MHC molecule expression, particularly class II E molecules, can influence T cell recognition and cytotoxicity.
Purpose of the Study:
- To investigate the specificity of cytolytic T lymphocytes (CTLs) generated against cell-surface E molecules.
- To determine if CTLs stimulated by E molecules can cross-react with cells lacking E molecules but expressing other MHC molecules.
- To explore the structural and functional relationship between H-2 class II A and E molecules.
Main Methods:
- Generation of cell-mediated lymphocytotoxicity in four mouse strain combinations differing in H-2 complex-controlled E molecule expression.
- Testing CTL reactivity against stimulator and non-stimulator cell lines.
- Blocking experiments using monoclonal antibodies specific for A or E molecules.
- Inhibition assays using 'cold targets' of different H-2 haplotypes (H-2f, H-2q).
Main Results:
- CTLs generated against E molecules showed cross-reactivity with E-negative cells expressing A molecules (H-2f and H-2q haplotypes).
- This cross-reactivity was blocked by antibodies against A molecules but not E or class I (K) molecules.
- Reciprocal inhibition between H-2f and H-2q targets indicated shared recognition determinants.
Conclusions:
- Cytolytic T lymphocytes stimulated by E molecules can recognize and lyse target cells expressing A molecules, even in the absence of E molecules.
- The observed E-A cross-reactivity supports a structural and functional relatedness between H-2 class II A and E molecules.
- These findings suggest a common evolutionary origin for the A- and E-encoding loci within the H-2 complex.