A single amino acid substitution in the Ak molecule fortuitously provokes an alloresponse

Paolo Dellabona, Bing Yuan Wei, Nadine Gervois, Christophe Benoist, Diane Mathis

Research output: Contribution to journalArticlepeer-review

Abstract

We discovered by chance that the R28 T cell hybridoma has dual specificity. It responds to a peptide derived from ribonuclease presented by cells displaying Ak molecules and it reacts, in the absence of added antigen, to cells expressing Ak complexes with a single amino acid substitution at position 69 of the α chain. Modelling and functional studies suggest that residue 69 is a peptide contact residue, prompting the hypothesis that R28's alloreactivity is a cross-reactive response to an unknown peptide bound in the 'groove' of the mutant Ak complex. In this report, we employ a competition assay to confirm that this alloresponse involves a groove-binding peptide, demonstrate that this peptide derives from or depends on fetal calf serum and exploit a panel of antigen-presenting cell lines - each displaying an Ak complex with a different position 69 substitution - to establish that the alloresponse is not just a heteroclitic response to ribonuclease, itself. We speculate that much of the alloreactivity against murine class II molecules that is revealed in vitro may prove to be directed at bovine serum-derived peptides, suggesting that in this context, alloreactivity is a misnomer.

Original languageEnglish
Pages (from-to)209-213
Number of pages5
JournalEuropean Journal of Immunology
Volume21
Issue number1
Publication statusPublished - Jan 1991

ASJC Scopus subject areas

  • Immunology

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