Minor H Antigens Introduced on H-2 Different Stimulating Cells Cross-React at the Cytotoxic T Cell Level during in Vivo Priming

The cellular basis of the cross-priming observed with minor histocompatibility antigens on H-2 different cells was investigated. Cytotoxic T cells induced against minor alloantigens show absolute H-2 restriction at the effector level ([51Cr]-release). That is, F1 (BALB/c X BALB.B) (H-2d/b) cytotoxic cells induced by immunization with B10(H-2b) cells are not able to lyse B10.D2(H-2d) targets. But an injection of B10 cells does prime F1 mice for a secondary cytotoxic response to B10.D2. The technique of inducing cytotoxic effector function polyclonally with Con A in the absence of alloantigen was used here to establish that such cross-priming reflects what happens at the cytotoxic cell level. It is shown that an F1 animal previously injected with B10 cells has expanded pools of memory cytotoxic cells reactive with B10 and B10.D2. From this it is concluded that: a) minor H structures on B10.D2 and B10 do cross-react at the cytotoxic T cell level during in vivo priming, and b) because normal cells cross-prime whereas tumor cells do not, then the F1 cytotoxic precursors are probably committed to respond to antigen on cells bearing either the maternal or paternal H-2 haplotype before they encounter antigen. Cross-priming may be explained by foreign minor H antigens being presented to F1 host T cells on the surface of host macrophages. Therefore priming is not restricted to the H-2 type of the injected cells but to both H-2 types of the F1 host.