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 [K(B)-D(B)] mice (B6) can be induced to respond to vaccinia virus in the context of both H-2K(K) and H-2D(B) when stimulated in B10.A(4R) [K(K)-D(B)] recipients. However, negatively selected B10.A(2R) [K(K)-D(B)] T cells respond to H-2D(B)-vaccinia virus but not to H-2K(B)-vaccinia virus when primed in an irradiated B6 environment. The B6 mouse strain is a high responder to vaccinia virus associated with H-2D(B), whereas the B10.A(2R) and B10.A(4R) recombinants are low responders. Responsiveness in the context of H-2D(B) is thus recognized when the only homology between T cell and recipient is at the H-2D locus and is suppressed when H-2K(K) is also present in both situations. The fact that negatively selected h-2K(B)-D(B) T cells can be induced to recognize H-2K(K)-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.