Reciprocal stimulation of negatively selected high-responder and low-responder T cells in virus-infected recipients.

Abstract

After depletion of alloreactive potential, immunologically naive T cells from C57BL/6J (Kb-Db) mice (B6) can be induced to respond to vaccinia virus in the context of both H-2Kk and H-2Db when stimulated in B10.A(4R) (Kk-Db) recipients. However, negatively selected B10.A(2R) (Kk-Db) T cells respond to H-2Db-vaccinia virus but not to H-2Kb-vaccinia virus when primed in an irradiated B6 environment. The B6 mouse strain is a high responder to vaccinia virus associated with H-2Db, whereas the B10.A(2R) and B10.A(4R) recombinants are low responders. Responsiveness in the context of H-2Db is thus recognized when the only homology between T cell and recipient is at the H-2D locus and is suppressed when H-2Kk is also present in both situations. The fact that negatively selected H-2Kb-Db T cells can be induced to recognize H-2Kk-vaccinia virus may reflect the existence of an "altered self" complex which is recognized via a single receptor, perhaps drawn from an alloreactive T-cell repertoire. At least in some instances, patterns of T-cell responsiveness are not totally constrained by the spectrum of H-2 antigens encountered in thymus.