Positive and negative selection of an antigen receptor on T cells in transgenic mice.
The T-cell repertoire found in the periphery is thought to be shaped by two developmental events in the thymus that involve the antigen receptors of T lymphocytes. First, interactions between T cells and major histocompatibility complex (MHC) molecules select a T-cell repertoire skewed towards recognition of antigens in the context of self-MHC molecules. In addition, T cells that react strongly to self-MHC molecules are eliminated by a process called self-tolerance. We have recently described transgenic mice expressing the alpha beta T-cell receptor from the cytotoxic T lymphocyte 2C (ref. 11). The clone 2C was derived from a BALB.B (H-2b) anti-BALB/c (H-2d) mixed lymphocyte culture and is specific for the Ld class I MHC antigen. In transgenic H-2b mice, a large fraction of T cells in the periphery expressed the 2C T-cell receptor. These T cells were predominantly CD4-CD8+ and were able to specifically lyse target cells bearing Ld. We now report that in the periphery of transgenic mice expressing Ld, functional T cells bearing the 2C T-cell receptor were deleted. This elimination of autoreactive T cells appears to take place at or before the CD4+CD8+ stage in thymocyte development. In addition, we report that in H-2s mice, a non-autoreactive target haplotype, large numbers of CD8+ T cells bearing the 2C T-cell receptor were not found, providing strong evidence for the positive selection of the 2C T-cell receptor specificity by H-2b molecules.
Sha
W C
WC
Howard Hughes Medical Institute, Washington University School of Medicine, Department of Medicine, St. Louis, Missouri 63110.
Nelson
C A
CA
Newberry
R D
RD
Kranz
D M
DM
Russell
J H
JH
Loh
D Y
DY
D000818:Animals; D030801:Animals, Genetically Modified; D000943:Antigens, Differentiation; D005434:Flow Cytometry; D006183:H-2 Antigens; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
D000943:Antigens, Differentiation; D006183:H-2 Antigens; D011948:Receptors, Antigen, T-Cell