Interaction of papain‐digested HLA class I molecules with human alloreactive cytotoxic T lymphocytes (CTL)
SUMMARY 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...
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Published in | Clinical and experimental immunology Vol. 91; no. 1; pp. 183 - 188 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.01.1993
Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | SUMMARY
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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0009-9104 1365-2249 |
DOI: | 10.1111/j.1365-2249.1993.tb03376.x |