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

• Published in: The Journal of immunology (1950) 2001-10, Vol.167 (7), p.3708-3714
• Main Authors: Maile, Robert, Wang, Bo, Schooler, Wesley, Meyer, Anthony, Collins, Edward J, Frelinger, Jeffrey A
• Format: Article
• Language: English
• Subjects: Animals; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Clonal Anergy; Female; Genes, T-Cell Receptor; Graft Rejection - immunology; Graft Survival; H-2 Antigens - administration & dosage; H-2 Antigens - immunology; H-Y Antigen - immunology; Histocompatibility Antigen H-2D; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Skin Transplantation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.7.3708

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-D(b) 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-D(b) 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-D(b) tetramer rejected B6 male skin grafts more rapidly than female littermates treated with irrelevant tetramer. In contrast, multiple doses of HY-D(b) tetramer did not further decrease graft survival. Rather, female B6 mice injected with multiple doses of HY-D(b) 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.