Expression and function of mutant Ia antigen in transgenic mice

Area of Science:

• Immunology
• Transgenic animal models
• MHC class II antigen presentation

Background:

• Cell surface expression of Ia antigens (MHC class II) depends on alpha and beta heterodimer assembly.
• Transgenic mice were created with wild-type Ak alpha and a mutant Ak beta (Ak beta MB) gene.

Purpose of the Study:

• To investigate the expression and function of a mutant Ia antigen beta chain in transgenic mice.
• To determine the role of the mutant Ia antigen in immune responses like allograft rejection and T cell development.

Main Methods:

• Generation of double transgenic mice carrying wild-type Ak alpha and mutant Ak beta (Ak beta MB) genes.
• Flow cytometry (FACS) analysis of lymphoid cells before and after lipopolysaccharide (LPS) stimulation.
• Allograft rejection studies using tail skin grafts from transgenic mice.
• Analysis of T cell populations (V beta 6+ T cells) in the thymus.

Main Results:

• The Ak alpha and Ak beta MB transgenes were initially not expressed on lymphoid cells.
• LPS stimulation induced Ak/Ak MB assembly and surface expression of the mutant Ia antigen.
• Tail skin grafts from transgenic mice were rejected by parental mice, indicating the mutant antigen's role in allograft rejection.
• Transgenic mice partially deleted V beta 6+ T cells, suggesting transgene product presence in the thymus.

Conclusions:

• The mutant Ak beta MB chain can assemble with Ak alpha and be expressed on the cell surface following appropriate stimulation.
• The mutant Ia antigen contributes to allograft rejection and influences T cell development in the thymus.
• This study provides insights into the assembly, expression, and immunologic function of mutant MHC class II molecules.