Unrestricted recognition of a nonpeptide antigen by CD8+ cytolytic T lymphocytes.
CD8+ murine CTL that are specific for an unusual nonpeptide Ag, the heme moiety of hemoglobin, have been derived by in vitro stimulation of spleen cells with hemin. Such CTL demonstrate a requirement for the expression of class I Ag on target cells, yet appear to be unrestricted to the extent that both syngeneic and allogeneic targets precoated with hemin are sensitive to lysis. A series of CTL clones with specificity for hemin was derived from C57BL/6 mice. They exhibited the same type of promiscuous recognition that was observed in CTL populations from a number of different strains. The possibility that hemin acts as a nonspecific mediator of lysis by CTL was ruled out by the fact that a variety of CTL populations and clones specific for different Ag did not exhibit hemin-specific lysis. Some explanations offered to explain these results include 1) the possibility that hemin is recognized by binding to a site on the MHC other than the Ag-binding groove, and 2) the possibility that TCR recognition of a rigid molecule, such as hemin, may be less sensitive to polymorphic variation in the MHC than is recognition of a conventional peptide Ag whose conformation may differ significantly when bound to MHC molecules whose sequences differ within the Ag-binding groove.
Sherman
L A
LA
Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
Lara
A M
AM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D000939:Epitopes; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D006418:Heme; D006427:Hemin