Journal of Experimental Medicine, Vol 142, 403-418, Copyright © 1975 by Rockefeller University Press
On the role of the H-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets
J Forman
Spleen cells cultured with syngeneic trinitrophenyl (TNP)-modified
stimulator cells display a cytotoxic effect against syngeneic TNP- modified
targets, but not against modified targets from unrelated H-2 haplotypes.
Targets that share the K and I region of the H-2 complex with the
stimulator (or effector) cell are lysed to the same extent as the specific
targets, while targets that share the I region only are not. When only the
D region is shared, a weak cytotoxic effect is observed. Therefore, the
stimulator (or effector) and target cell must share the K or D but not the
I region of the H-2 complex in order for optimal cytotoxicity to occur.
Spleen cells sensitized to irradiated TNP-modified H-2-allogeneic cells are
cytotoxic to these specific cells. Coculture of F1 hybrid cells with
irradiated TNP-modified parental cells result in a cytotoxic effect against
only those specific parental cells and not TNP-modified cells from the
other parent. The cytotoxic effect of the F1 effector cells in the
cell-mediated lympholysis test is blocked by the addition of unlabeled
TNP-modified targets that are H-2 syngeneic with the sensitizing parental
strain, but not H-2 syngeneic with the other parental strain. These data
demonstrate that the specificity of the effector cell in this syngeneic
cytotoxicity system is directed against altered self H-2-controlled- gene
products, rather than a requirement for sharing of histocompatibility genes
between effector and target cell in order for lysis to occur. The role of
H-2 antigens in determining the sensitivity of a target cell to
T-cell-mediated lysis is discussed.
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