T cells that encounter virus in the complete absence of a particular H-2 antigen are nonresponsive when stimulated again in the context of that H-2 antigen.

Immunologically naive BALB/c (H-2d) and C57BL/6J (B6) (H-2b) T-cell populations can, after filtration to remove alloreactive precursor lymphocytes, be induced to respond to vaccinia virus presented in the context of H-2Kk when stimulated in an appropriate recipient. Exposure to vaccinia virus 6 wk previously completely abrogated the capacity of BALB/c T cells to interact with H-2Kk-vaccinia virus. This is also true for negatively selected B6 thoracic duct lymphocytes taken at 14 or 18 d, but not at 6 wk after immunization: the discrepancy is thought to reflect the progressive emergence of new T cells in the latter group. No evidence could be found for the operation of suppression, and the results are considered to indicate that T cells that interact with virus in the absence of the relevant H-2 antigen are tolerized. Whereas stimulation to effector function is H-2 restricted, induction of immune paralysis may be unrestricted. The capacity of T-cell populations to respond to virus presented in the context of allogeneic H-2 determinants thus depends upon previous antigenic experience.