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Positive selection determines T cell receptor V beta 14 gene usage by CD8+ T cells
N S Liao1, J Maltzman, D H Raulet
1Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
The Journal of Experimental Medicine
|July 1, 1989
Summary
A new antibody, 14-2, reveals T cell receptor (TCR) V beta 14 usage varies by T cell type and is H-2 gene controlled. This suggests H-2-dependent positive selection influences TCR selection.
Area of Science:
- Immunology
- T cell biology
- Molecular genetics
Background:
- T cell receptors (TCRs) mediate adaptive immunity by recognizing antigens.
- TCR variable beta (V beta) chains play a crucial role in TCR specificity and repertoire formation.
- The Major Histocompatibility Complex (MHC) class I molecules, encoded by H-2 genes in mice, are critical for T cell selection.
Purpose of the Study:
- To characterize a novel monoclonal antibody (mAb), 14-2, that recognizes TCRs containing the V beta 14 gene segment.
- To investigate the frequency of V beta 14+ T cells within CD4+ and CD8+ T cell subsets across different mouse strains.
- To determine the role of H-2 genes and positive selection in the regulation of V beta 14 usage in T cells.
Main Methods:
- Flow cytometry using mAb 14-2 to quantify V beta 14+ T cells in CD4+ and CD8+ subsets.
- Analysis of T cell populations in various mouse strains with different H-2 haplotypes.
- Radiation chimera experiments to study T cell development and positive selection.
Main Results:
- The frequency of V beta 14+ T cells differs significantly between CD4+ and CD8+ T cell subsets and is controlled by H-2 genes.
- CD8+ T cells from H-2b mice had ~2.3% V beta 14+ T cells, while those from K kappa-expressing mice had >8%.
- CD4+ T cells consistently showed 7-8% V beta 14 expression across strains.
- Radiation chimeras demonstrated preferential positive selection of V beta 14+ CD8+ T cells in K kappa-expressing mice.
Conclusions:
- H-2-dependent positive selection of T cells occurs in unmanipulated mice.
- The V beta domain of the TCR can strongly influence positive selection and H-2 restriction, potentially independent of beta-junctional sequences and the alpha chain.