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-2(b) x H-2(d))F1 mice were constructed that carry integrated copies of a modified H-2K(k) gene resulting in the secretion from various cell types including thymocytes of soluble H-2K(k) molecules. Despite the presence of H-2K(k) antigen, these mice were still able to generate an H-2K(k)-specific T-cell response. This response was comparable to that produced by normal littermates when stimulated with cells expressing membrane H-2K(k) in a mixed lymphocyte reaction. In contrast, only transgenic mice failed to generate a cytolytic T-cell response to soluble H-2K(k) antigen expressed by recombinant vaccinia virus and presented by the H-2D(b) 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.