Positive selection of an MHC class-I restricted TCR in the absence of classical MHC class I molecules.
The H-2Ld alloreactive 2C T cell receptor (TCR) is commonly considered as being positively selected on the H-2Kb molecule. Surprisingly, 2C TCR+ CD8+ single-positive T cells emerge in massive numbers in fetal thymic organ culture originating from 2C transgenic, H-2KbD(b-/-) (2C+KbD(b-/-)) but not in fetal thymic organ culture from beta2-microglobulin(-/-) 2C transgenic animals. Mature CD8+ T cells are observed in newborn but not in adult 2C+KbD(b-/-) mice. These CD8+ T cells express the alpha4beta7 integrin, which allows them to populate the intestine, a pattern of migration visualized by intrathymic injection of FITC and subsequent accrual of FITC-labeled lymphocytes in the gut. We conclude that the 2C TCR is reactive not only with H-2Ld and H-2Kb, but also with nonclassical MHC class I products to enable positive selection of 2C+ T cells in the fetal and newborn thymus and to support their maintenance in the intestine.
Maurice
M M
MM
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Gould
D S
DS
Carroll
J
J
Vugmeyster
Y
Y
Ploegh
H L
HL
D000818:Animals; D000831:Animals, Newborn; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003433:Crosses, Genetic; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D064532:Histocompatibility Antigen H-2D; D011948:Receptors, Antigen, T-Cell; D001613:beta 2-Microglobulin