Interaction of papain-digested HLA class I molecules with human alloreactive cytotoxic T lymphocytes (CTL)

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Abstract
Acute immunological rejection events of transplanted allogeneie organs are strongly dependent on T cell reactivity against foreign MHC products. The recognition requirements of alloreactive cytotoxic T cells arc of particular interest for finding approaches to modulating allorcactivity. The role of the allogeneic MHC molecule itself and/or an associated peptide in the interaction with the T cell receptor is still, however, unclear. Our studies have focused on the interactions of papain-digested HLA class I molecules with alloreactivc CD8+ CTL. These polypeptidcs, consisting of the polymorphic α1 and α2 and the monomorphic α3 domains, were used in both soluble and immobilized form to study their functional effects on anti-HLA-A2 reactive CTL. Purified polypeptides were of molecular mass 32–34 kD. HLA-A2 polypcptides (0–55 μg/ml) in soluble form induced half-maximal reduction of CTL cytotoxicity. These concentrations were quantitatively comparable to the effective doses of intact HLA class I molecules, which contain the hydrophobic transmembrane domain and the intracytoplasmic tail. In addition, specific activation requirements of these CTL were investigated in a serine esterasc release assay. Maximal degranulation was observed after 2 h of antigen contact. Purified HLA class I molecules allospccifically activated the anti-HLA-A2 CTL to degranulate serine esterase, when immobilized on plastic microtitre plates. Thus, polypeptidcs containing the polymorphic αl and α2 domains of human class I molecules potentially modulate the cytotoxic T cell response. This might have implications for the reduction or prevention of allograft rejection in recipients of foreign organs.