Investigation of peptide involvement in T cell allorecognition using recombinant HLA class I multimers

Alison M.E. Whitelegg, Liesbeth E.M. Oosten, Susan Jordan, Michel Kester, Astrid G.S. Van Halteren, J. Alejandro Madrigal, Els Goulmy, Linda D. Barber

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

24 Citaten (Scopus)


Alloreactive T cells are involved in injurious graft rejection and graft-vs-host disease. However, they can also evoke beneficial responses to tumor Ags restricted by foreign MHC molecules. Manipulation of these alloreactivities requires information on the basis of T cell allorecognition. The vigorous T cell response to foreign MHC molecules may arise from peptide-independent recognition of polymorphic residues of foreign MHC molecules or peptide-specific recognition of novel peptides presented by foreign MHC molecules. We investigated CD8+ T cell allorecognition using recombinant HLA class I/peptide complexes. Peptide-specific allorecognition was examined using tetramers of HLA-A*0201 representing five peptides derived from ubiquitously expressed self-proteins that are known to bind endogenously to HLA-A*0201. Distinct subsets of CD8+ T cells specific for each HLA-A*0201/peptide combination were detected within four in vitro-stimulated T cell populations specific for foreign HLA-A*0201. Peptide-independent allorecognition was investigated using artificial Ag-resenting constructs (aAPCs) coated with CD54, CD80, and functional densities of a single HLA-A*0201/peptide combination for four different peptides. None of the four T cell populations specific for foreign HLA-A*0201 were stimulated by the aAPCs, whereas they did produce IFN-γ upon stimulation with cells naturally expressing HLA-A*0201. Thus, aAPCs did not stimulate putative peptide-independent allorestricted T cells. The results show that these alloreactive populations comprise subsets of T cells, each specific for a self-peptide presented by foreign class I molecules, with no evidence of peptide-independent components.

Originele taal-2Engels
Pagina's (van-tot)1706-1714
Aantal pagina's9
TijdschriftJournal of Immunology
Nummer van het tijdschrift3
StatusGepubliceerd - 1 aug. 2005
Extern gepubliceerdJa


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