Physiologic expression of two superantigens in the BDF1 mouse

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Endogenous superantigens in mice, including Mls loci, are primarily encoded by mouse mammary tumor proviruses (Mtv).
• Differences in stimulatory capacity exist between viral superantigens, such as Mls-1a (Mtv-7) and Etc-1 (Mtv-9).

Purpose of the Study:

• To investigate the physiological expression and presentation of Mls-1a and Etc-1 superantigens.
• To understand the cellular mechanisms regulating superantigen presentation and T cell deletion.

Main Methods:

• Utilized T cell hybridomas (1BVB11.40 anti-Etc-1, 18bbm.19 anti-Mls-1a).
• Studied superantigen presentation by various antigen-presenting cells (B cells, macrophages, dendritic cells) from BDF1 mice.
• Investigated the effects of LPS and IL-4 on superantigen presentation by B cells.
• Examined T cell clonal deletion in B cell-depleted neonatal BDF1 mice.

Main Results:

• B cells from spleen and thymus present both Etc-1 and Mls-1a superantigens; macrophages and dendritic cells do not.
• LPS or IL-4 treatment significantly enhances presentation of Mls-1a and Etc-1 by small, resting B cells, with synergistic effects observed.
• Depletion of neonatal B cells prevents clonal deletion of Etc-1-reactive T cells (V beta 5+, 11+) but not Mls-1a-reactive T cells (V beta 6+, 8.1+).

Conclusions:

• Mls-1a and Etc-1 superantigens are expressed on similar cell types and their presentation is similarly regulated by agents affecting B lymphocytes.
• Differences in stimulatory potency between superantigens likely stem from variations in the avidity of the T cell receptor V beta domain for the MHC class II/superantigen ligand.