MHC class I expression and CD8+ T cell development in TAP1/beta 2-microglobulin double mutant mice

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Transporter associated with antigen processing 1 (TAP1) and beta 2-microglobulin (beta 2m) are crucial for presenting antigens via MHC class I molecules.
• Disruptions in TAP1 or beta 2m affect the surface expression of MHC class I subunits, impacting T cell responses.

Purpose of the Study:

• To investigate the consequences of combined TAP1 and beta 2m gene disruptions on MHC class I expression and T cell immunity.
• To determine if residual MHC class I on the cell surface can support T cell repertoire selection and function.

Main Methods:

• Generation of homozygous TAP1/beta 2m double knockout ( -/- ) mice.
• Analysis of MHC class I surface expression using immunofluorescence and immunoprecipitation.
• Assessment of CD8+ cytotoxic T cell (CTL) responses and skin graft rejection in knockout mice.

Main Results:

• Surface expression of H-2Kb and Db was undetectable in TAP1/beta 2m -/- mice.
• Despite undetectable surface MHC I, TAP1/beta 2m -/- cells elicited CD8+ CTL responses and were recognized by allospecific CTL.
• TAP1/beta 2m -/- mice exhibited CD4-CD8+ T cells and rapidly rejected skin grafts, indicating functional T cell populations.

Conclusions:

• Very low levels of MHC class I heavy chains can reach the cell surface in TAP1/beta 2m -/- cells.
• These residual MHC I molecules are sufficient for positive selection of the CD8+ T cell repertoire.
• Functional CD8+ T cell responses, including allospecific CTL activity, can occur even with complete absence of TAP1 and beta 2m.