Selection of cytotoxic T-cell precursors specific for minor histocompatibility determinants. I. Negative selection across H-2 barriers induced with disrupted cells but not with glutaraldehyde-treated cells: evidence for antigen processing.
Intravenous injection of CBA mice with H-2-compatible irradiated B10.BR spleen cells led to a sequence of negative and positive selection of the host T-cell response against the multiple foreign minor histocompatibility antigens (HA) on the injected cells. By 1 d posttransfer, thoracic duct lymphocytes (TDL) of the host had lost the capacity to differentiate in vitro into cytotoxic cells specific for the injected minor HA; spleen and lymph node cells, by contrast, gave normal or enriched responses at this time. By 5 d posttransfer, TDL were hyperresponsive to the injected antigens. Selection with disrupted (sonicated) cells gave similar findings. With injection of either irradiated of disrupted spleen cells, the H-2 haplotype of the minor HA-bearing cells had no apparent effect on the magnitude of selection. By contrast, treatment of spleen cells with glutaraldehyde before injection led to H-2 restriction of selection, i.e., negative selection of the CBA response to B10.BR was marked with injection of glutaraldehyde-treated H-2-compatible B10.BR cells but was minimal with H-2-different B10 or B10.D2 cells. These data are taken to imply that, at least in H-2-incompatible situations, the minor HA-bearing cells must be processed by host cells, i.e., to allow the antigens to become associated with self H-2 determinants. Circumstantial evidence from studies on the specificity of selection induced with glutaraldehyde-treated cells from mice of the B10 recombinant strains suggested that I region-restricted T cells may control the induction of H2K, D-restricted cytotoxic precursor cells.
D000818:Animals; D002458:Cell Fractionation; D002642:Chick Embryo; D002874:Chromosome Mapping; D003602:Cytotoxicity, Immunologic; D005802:Genes, MHC Class II; D005976:Glutaral / Q000494:pharmacology; D006183:H-2 Antigens; D006649:Histocompatibility Antigens / Q000008:administration & dosage / Q000528:radiation effects; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D005976:Glutaral