Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane-bound alloantigen

The properties of transmembrane and soluble transplantation
antigens were compared with respect to the induction of tolerance
and the selection of the T-cell repertoire. For this purpose,
transgenic (H-2b x H-2d)F1 mice were constructed that carry
integrated copies of a modified H-2Kk gene resulting in the
secretion from various cell types including thymocytes of soluble
H-2Kk molecules. Despite the presence of H-2Kk antigen, these mice
were still able to generate an H-2Kk-specific T-cell response. This
response was comparable to that produced by normal littermates when
stimulated with cells expressing membrane H-2Kk in a mixed
lymphocyte reaction. In contrast, only transgenic mice failed to
generate a cytolytic T-cell response to soluble H-2Kk antigen
expressed by recombinant vaccinia virus and presented by the H-2Db
molecule. These data imply the presence of two populations of
alloreactive cytolytic T cells. A small fraction of T cells
recognizes alloantigen as antigenic peptide(s) presented by other
major histocompatibility complex class I molecules and tolerance
can be induced in this population by soluble alloantigen. The
majority of T cells, however, require the whole cell
membrane-expressed class I molecule for recognition. This
population is not affected by tolerance induction to the soluble
major histocompatibility complex class I molecule.