Multivalent Requirement for the Stimulation of Alloreactive T Cells: Studies with Engineered Soluble MHC Class I Proteins In Vitro and In Vivo

Abstract

The murine class I major histocompatibility antigens play critical roles in the interaction of class I-restricted T cell receptors with their stimulatory or target antigen presenting cells. One approach taken by our laboratories has been to investigate the biological activity of genetically engineered, soluble, homogenous, purified class I molecules in the stimulation and inhibition of allospecific T cell hybridomas (Margulies et al, 1986; McCluskey et al, 1988; Schneck et al, 1989a). More recently we have established a system for comparing the role of the cell surface multivalent display of the MHC molecule with these monovalent soluble analogues expressed in vivo in transgenic mice. In this brief review, we hope to recount the logic by which the initial soluble class I MHC molecules were generated, summarize previously published as well as unpublished data on their expression and function, and present some preliminary evidence suggesting that transgenic mice expressing soluble analogues of the H-2D^d protein in a C57B1/6 background will be useful for studies of the molecular and biochemical basis of the generation of immunological tolerance to class I molecules.