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The Journal of Immunology, 2001, 167: 3708-3714.
Copyright © 2001 by The American Association of Immunologists

Antigen-Specific Modulation of an Immune Response by In Vivo Administration of Soluble MHC Class I Tetramers1

Robert Maile2,*, Bo Wang*, Wesley Schooler{dagger}, Anthony Meyer{dagger}, Edward J. Collins*,{ddagger} and Jeffrey A. Frelinger*

Departments of * Microbiology and Immunology, {dagger} Surgery, and {ddagger} Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599

Soluble MHC/peptide tetramers that can directly bind the TCR allow the direct visualization and quantitation of Ag-specific T cells in vitro and in vivo. We used HY-Db tetramers to assess the numbers of HY-reactive CD8+ T cells in HYTCR-transgenic mice and in naive, wild-type C57BL/6 (B6) mice. As expected, tetramer staining showed the majority of T cells were male-specific CD8+ T cells in female HY-TCR mice. Staining of B6 mice showed a small population of male-specific CD8+ T cells in female mice. The effect of administration of soluble MHC class I tetramers on CD8+ T cell activation in vivo was unknown. Injection of HY-Db tetramer in vivo effectively primed female mice for a more rapid proliferative response to both HY peptide and male splenocytes. Furthermore, wild-type B6 female mice injected with a single dose of HY-Db tetramer rejected B6 male skin grafts more rapidly than female littermates treated with irrelevant tetramer. In contrast, multiple doses of HY-Db tetramer did not further decrease graft survival. Rather, female B6 mice injected with multiple doses of HY-Db tetramer rejected male skin grafts more slowly than mice primed with a single injection of tetramer or irradiated male spleen cells, suggesting clonal exhaustion or anergy. Our data highlight the ability of soluble MHC tetramers to identify scarce alloreactive T cell populations and the use of such tetramers to directly modulate an Ag-specific T cell response in vivo.




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