T cell development in TCR-alpha beta transgenic mice. Analysis using V(D)J recombination substrates

Area of Science:

• Immunology
• T cell differentiation
• Molecular biology

Background:

• Intrathymic T cell differentiation progresses from CD4-8- (DN) precursors to CD4+8- or CD4-8+ (SP) lymphocytes.
• Functionally rearranged T cell receptor (TCR) transgenes can influence thymocyte development and selection processes.

Purpose of the Study:

• To investigate how transgenic TCR (Tg-TCR) expression affects V(D)J recombination during T cell development.
• To analyze the impact of a specific MHC class I allospecific TCR transgene (KB5C20) on thymocyte differentiation.

Main Methods:

• Generation of double transgenic mice carrying V(D)J recombination substrates and the KB5C20 Tg-TCR.
• Analysis of V(D)J recombination substrate rearrangements in purified Tg-TCR+ thymocyte populations under positive and negative selection conditions.

Main Results:

• Positively selected SP thymocytes expressing the Tg-TCR showed minimal impact on V(D)J recombination.
• Tg-TCR+ DN thymocytes exhibited premature cessation of V(D)J recombination, irrespective of selection haplotype.
• This recombination profile in Tg-TCR+ DN cells persisted in peripheral cells and differed from other DN subsets.

Conclusions:

• The KB5C20 Tg-TCR minimally affects V(D)J recombination in developing SP T cells along the major alpha beta pathway.
• Tg-TCR expression in DN thymocytes leads to an early halt in V(D)J recombination, suggesting alternative differentiation routes.
• These findings provide insights into the origin and differentiation of Tg-TCR+ DN and SP thymocytes.