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GENETIC FACTORS IN THE STIMULATION OF T CELL RESPONSES AGAINST ECTROMELIA VIRUS‐INFECTED CELLS: ROLE OF H‐2K, H‐2D AND H‐2I GENES
Author(s) -
Pang T,
Blanden RV
Publication year - 1977
Publication title -
australian journal of experimental biology and medical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0004-945X
DOI - 10.1038/icb.1977.54
Subject(s) - cytotoxic t cell , biology , ectromelia virus , in vitro , antigen , antigen presenting cell , population , virus , virology , t cell , immune system , gene , microbiology and biotechnology , immunology , recombinant dna , genetics , medicine , environmental health , vaccinia
Summary When virus‐immune cytotoxic T cells were generated in secondary responses in vitro to syngeneic, infected stimulator cells, they only killed infected targets that shared H‐2K or H‐2D genes with the T cells and stimulator cells. H‐2I region compatibility was neither sufficient nor necessary. The role of H‐2K, H‐2D and H‐2I genes in the interaction between memory T cells and infected stimulator cells was then investigated. Initial attempts failed because of escape of virus into the responder population. Steps were taken to eliminate this problem; confirming their efficacy was the finding that when (CBA/H × BALB/c) F 1 memory T cells were stimulated by either parental type, the cytotoxic T cells generated only killed the target cell type syngeneic to the stimulator cell used to induce the response. Using recombinant strain macrophages as infected stimulator cells, it was further shown that K or D region sharing between stimulator and responder cells was sufficient to induce the response. I region homology, on the other hand, although stimulating high levels of 3 H‐thymidine incorporation, did not give rise to significant amounts of cytotoxic activity against virus‐infected target cells. These results are compatible with the interpretation that the inductive signal to cytotoxic T cell precursors (memory T cells) in the in vitro secondary response is an antigenic pattern containing virus‐induced and self H‐2K or H‐2D components; the response of the cytotoxic cells may be facilitated by a “helper”, DNA‐synthesizing subclass which responds to antigenic patterns containing both virus‐induced and I region‐determined components. Evidence from cytotoxic T cell induction with semi‐compatible infected macrophages shows that H‐2K (or H‐2D ) antigens and viral antigen must be in the same cell membrane for efficient stimulation to occur. This suggests that both the antigens, and the T cell receptors for them, are closely associated in the infected cell and T cell membranes respectively.