Antigen-specific modulation of an immune response by in vivo administration of soluble MHC class I tetramers.
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.
Maile
R
R
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA. robmaile@bellsouth.net
Wang
B
B
Schooler
W
W
Meyer
A
A
Collins
E J
EJ
Frelinger
J A
JA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D017635:Clonal Anergy; D005260:Female; D019672:Genes, T-Cell Receptor; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006183:H-2 Antigens / Q000008:administration & dosage / Q000276:immunology*; D006182:H-Y Antigen / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016038:Skin Transplantation
D006183:H-2 Antigens; D006182:H-Y Antigen; D064532:Histocompatibility Antigen H-2D