Interaction of papain-digested HLA class I molecules with human alloreactive cytotoxic T lymphocytes (CTL).
Acute immunological rejection events of transplanted allogeneic organs are strongly dependent on T cell reactivity against foreign MHC products. The recognition requirements of alloreactive cytotoxic T cells are of particular interest for finding approaches to modulating alloreactivity. 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 alloreactive CD8+ CTL. These polypeptides, consisting of the polymorphic alpha 1 and alpha 2 and the monomorphic alpha 3 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 polypeptides (0.55 micrograms/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 esterase release assay. Maximal degranulation was observed after 2 h of antigen contact. Purified HLA class I molecules allospecifically activated the anti-HLA-A2 CTL to degranulate serine esterase, when immobilized on plastic microtitre plates. Thus, polypeptides containing the polymorphic alpha 1 and alpha 2 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.
Hausmann
R
R
Institute of Immunology, University of Kiel, Germany.
Zavazava
N
N
Steinmann
J
J
Müller-Ruchholtz
W
W
D003602:Cytotoxicity, Immunologic; D015789:HLA-A2 Antigen / Q000276:immunology; D015793:HLA-B7 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010206:Papain / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D015395:Histocompatibility Antigens Class I; D010206:Papain