Transplantation antigens per se are poor immunogens within a species

Abstract

THE structure of HLA substances make it surprising that they provoke strong alloimmune responses^1–3. They are composed of two chains, one invariant within the species, and the other bearing a single determinant defined by monospecific HLA sera⁴, or a few determinants defined by polyspecific sera^4,5, and thus most closely resemble haptens on non-immunogenic carriers. If this is true generally of antigens determined by major histocompatibility systems (MHC), they could be expected to be poorly or non-immunogenic within a species. This, however, conflicts with the evidence that when present on viable tissue grafts, these antigens provoke strong humoral and cellular alloimmune responses^6–8. But there is also evidence that their immunogenicity depends on additional factors^9,10. Here, we present data which reconcile these seemingly conflicting lines of evidence, by showing that the induction of primary immune responses (humoral and cellular) against MHC antigens in vivo depends both on the presentation of alloantigen and on a second signal provided by a live cell. Without the latter, the small quantities of MHC antigen present on conventional allografts would not induce primary immunity.