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CYTOTOXIC T CELL RECOGNITION OF ECTROMELIA VIRUS‐INFECTED CELLS.
Author(s) -
Blanden Robert V,
Pang Tikky
Publication year - 1978
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.1978.8
Subject(s) - cytotoxic t cell , ectromelia virus , biology , antigen , virology , virus , immune system , t cell , in vitro , microbiology and biotechnology , immunology , genetics , vaccinia , gene , recombinant dna
Summary Virus‐immune memory T cells from A.TL mice (K 8 , D d ) stimulated in vitro by ectromelia‐infected BALB/c macrophages (K d , D d ) gave rise to the subset of cytotoxic T cells that recognized virus plus H‐2D d and lysed infected BALB/c, not infected SJL/J ( K 8 , D 8 ) targets, despite cultural conditions which ensured that the responding A.TL cells were also in contact with the H‐2K 8 antigen (on other, adjacent A.TL cells). The converse results were obtained using SJL/J infected stimulators. Thus, it seemed that viral and H‐2K or H‐2D antigens must be in the same cell surface membrane, probably in physical association, to produce antigen moieties that stimulated virus‐immune T cells, These results implied that functional pairs of hypothetical recognition structures for viral and H‐2 determinants would need to be associated in some way in the memory T cell membrane. A second experimental approach further explored this hypothesis. C57BL/6 and B6.C‐ H‐2 ba mice differ because of a gain‐loss mutation in the H‐2K region, apparently in a cistron coding for an H‐2K b polypeptide antigen. Mutant and wild‐type share H‐2K b determinant(s) recognizable by allogeneic cytotoxic T cells, in addition to possessing unique determinant(s) defined by the mutation. Virus‐immune cytotoxic T cells, syngeneic with respect to infected stimulator cells, apparently recognize the unique determinant (s) but are not stimulated by. or do not recognize the shared determinant(s). despite the presence of the latter on virus‐infected cells as demonstrated by lysis of infected targets by mixed lymphocyte reactions (MLR)‐generated T cells directed only at the shared determinants. These results are discussed in terms of two alternative, but not mutually exclusive, hypotheses. The first suggests that physical association between viral and H‐2K molecules may result in certain H‐2K determinants being “masked” or inaccessible to T cell receptors, thus rendering them unable to stimulate T cell responses. It would again follow that the T cell recognition structures for viral and H‐2 determinants would also need to be associated in some way. An alternative is that the shared determinants revealed by the cross‐reactivity of allogeneic cytotoxic T cells generated in MLR are not encompassed in the dictionary of receptors on syngeneic T cells that recognize, and are stimulated by, virus‐infected self cells.