Peptide contributes to the specificity of positive selection of CD8+ T cells in the thymus.

Ashton-Rickardt PG, Van Kaer L, Schumacher TN, Ploegh HL, Tonegawa S
Cell. 1993 73 (5): 1041-9

PMID: 8500174 · DOI:10.1016/0092-8674(93)90281-t

Mice deficient in the gene encoding the peptide transporter associated with antigen processing (TAP1) have drastically reduced levels of surface expression of MHC class I molecules and few CD8+ T cells. Addition of class I binding peptides to cultured fetal thymi from TAP1 mutant mice invariably allowed the rescue of class I expression, while only some of these peptides promoted the positive selection of CD8+ T cells, which were polyclonal and specific for the peptide-MHC complex. A nonselecting peptide was converted to a mixture of selecting peptides when the residues involved in the interaction with TCRs were altered. A mixture of self-peptides derived from C57BL/6 thymi induced positive selection of CD8+ T cells at concentrations that gave relatively low class I surface expression. The implication of these observations is that self-peptides determine, in part, the repertoire of specificities exhibited by CD8+ T cells.

MeSH Terms (16)

Amino Acid Sequence Animals ATP-Binding Cassette Transporters ATP Binding Cassette Transporter, Subfamily B, Member 2 Carrier Proteins CD8 Antigens Histocompatibility Antigens Class I Histocompatibility Antigens Class II Mice Mice, Inbred C57BL Mice, Mutant Strains Molecular Sequence Data Organ Culture Techniques Peptides T-Lymphocytes Thymus Gland

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