Increase in positive selection of CD8+ T cells in TAP1-mutant mice by human beta 2-microglobulin transgene.
Mice harboring a deletion of the gene encoding the transporter associated with antigen presentation-1 (TAP1) are impaired in providing major histocompatibility complex (MHC) class I molecules with peptides of cytosolic origin and lack stable MHC class I cell surface expression. They consequently have a strongly reduced number of CD8+ T cells. To examine whether selection of CD8+ T cells is dependent on TAP-dependent peptides, we partially restored MHC class I cell surface expression in TAP1-deficient mice by introduction of human beta 2-microglobulin. We show that selection of functional CD8+ T cells can be augmented in vivo in the absence of TAP1-dependent peptides.
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
H
H
Martien van Santen
A
A
Woolsey
P G
PG
Rickardt
L
L
Van Kaer
E J
EJ
Baas
A
A
Berns
S
S
Tonegawa
H L
HL
Ploegh
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000502:physiology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000941:Antigens; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin