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Related Experiment Videos

Ek beta mutant antigen-presenting cell lines expressing altered Ak alpha molecules.

H Quill, R H Schwartz, L H Glimcher

    Journal of Immunology (Baltimore, Md. : 1950)
    |May 1, 1986
    PubMed
    Summary

    Mutant antigen-presenting cells (APCs) reveal that changes in Ia molecules selectively impact T cell recognition. These findings suggest individual Ia molecules have distinct functional sites for antigen presentation.

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    Area of Science:

    • Immunology
    • Molecular Biology
    • Cell Biology

    Background:

    • Antigen-presenting cells (APCs) are crucial for initiating adaptive immune responses.
    • Molecules like MHC class II (Ia) on APCs present antigens to T cells.
    • Understanding Ia molecule function is key to deciphering immune regulation.

    Purpose of the Study:

    • To investigate the functional consequences of mutations in Ia molecules on antigen presentation.
    • To analyze how alterations in specific Ia chains affect T cell recognition.
    • To explore the structural and functional domains of Ia molecules.

    Main Methods:

    • Chemical mutagenesis of TA3 cells to generate mutant APCs.
    • Negative immunoselection to isolate cells with altered Ek beta molecules.

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  • Analysis of Ia molecule biosynthesis, assembly, and surface expression.
  • Assays of antigen-presenting function using various T cell clones.

    • Main Results:

    • Three types of Ia mutants were identified based on Ek beta and Ak alpha chain expression and reactivity.
    • Mutations affecting Ak alpha chains often co-occurred with altered or lost Ek beta expression.
    • Selective T cell responses were observed, with some T cell clones responding to specific mutant APCs while others did not.
    • Autoreactive T cell hybridomas showed reduced stimulation by APCs with modified Ak alpha proteins.

    Conclusions:

    • Ia molecule mutations can have highly selective effects on antigen presentation to T cells.
    • Alterations in Ia molecules impact both T cell recognition and monoclonal antibody binding.
    • These findings suggest that individual Ia molecules comprise multiple distinct functional subsites.