Journal of Experimental Medicine, Vol 144, 933-945, Copyright © 1976 by Rockefeller University Press
H-2 restriction of virus-specific cytotoxicity across the H-2 barrier. Separate effector T-cell specificities are associated with self-H-2 and with the tolerated allogeneic H-2 in chimeras
RM Zinkernagel
During infection with lymphocytic choriomeningitis or vaccinia virus, F1
irradiation chimeras reconstituted with bone marrow cells from or both
parents generate cytotoxic T cells which can lyse targets across the H-2
barrier. However, activity of chimera T cells is H-2 restricted as shown by
cold target competition experiments and selective restimulation of a
secondary response in vitro; T cells of H-2k specificity which lyse
tolerated infected H-2d target cells do not lyse infected H-2k or unrelated
target cells and vice versa. Therefore, H-2 restriction of virus-specific
cytotoxic T cells probably does not reflect need for like-like
self-interactions for lysis to occur. The specificity of virus immune T
cells is thus determined by the H-2K and H-2D specificities present in the
infected animal and which are probably recognized unidirectionally by T
cells. The results are compatible with the idea the T cells are specific
for "altered alloantigen", i.e., a complex of cell surface marker and viral
antigen. Alternatively, explained with a dual recognition model, T cells
may possess two independently, clonally expressed receptors, a self-
recognizer which is expressed for one of the syngeneic or tolerated
allogeneic K or D "self" markers, and an immunologically specific receptor
for viral antigen.
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