Characterization of the ligand(s) responsible for negative selection of V beta 11- and V beta 12-expressing T cells: effects of a new Mls determinant

Abstract

During T cell development, events occur that result in the generation of a T cell population capable of recognizing foreign antigens in association with self major histocompatibility complex (MHC) gene products. However, selective events also occur during thymic education that result in the deletion of T cells expressing alpha/beta T cell receptors with high affinity for self determinants alone, i.e., potentially self-reactive T cells. Both MHC- and non-MHC-encoded self antigens appear to play critical roles in this negative selection of self-reactive T cells. We recently observed that T cells expressing V beta 5, V beta 11, V beta 12, or V beta 16 products are deleted in most strains of H-2k type, but not in congenic H-2b strains. In contrast, the H-2k strain C58/J deleted V beta 5+ and V beta 16+ T cells, but failed to delete T cells expressing V beta 11 or V beta 12. Based upon this observation, in the present study we have analyzed the genetic regulation of the ligands responsible for deletion of V beta 11- and V beta 12-expressing T cells, and have tested the possibility that these ligands can function as strong alloantigens analogous to the known minor lymphocyte stimulatory (Mls)- and MHC-encoded antigens. Two major findings have resulted from these studies. First, the ligands recognized by V beta 11+ and V beta 12+ T cells were regulated by both MHC- and multiple non-MHC-encoded genes. Correlation between expression of these two V beta s in backcross animals suggested that shared, though not necessarily identical, ligands mediate deletion of V beta 11- and V beta 12-expressing T cells. Second, the ligand for deletion of V beta 11- and V beta 12-expressing T cells functions as a newly defined Mls alloantigen that stimulates primary proliferative responses in T cell populations from mice that express V beta 11+ and V beta 12+ T cells.