Journal of Experimental Medicine, Vol 169, 1655-1668, Copyright © 1989 by Rockefeller University Press

ARTICLES

I-A alpha polymorphic residues that determine alloreactive T cell recognition

M Pierres, S Marchetto, P Naquet, D Landais, J Peccoud, C Benoist and D Mathis
Centre d'Immunologie Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique de Marseille- Luminy, France.

An individual's T lymphocytes are highly reactive to allogeneic MHC molecules. As a step in deciphering the mechanism of allorecognition by T lymphocytes, we have attempted to identify the TCR's target on MHC class II molecules, in particular the polymorphic residues that determine the specificity of recognition. We have generated a panel of Ak-reactive, Ab-nonreactive T cell hybridomas, and sets of L cell transfectants displaying A alpha A beta molecules with wild-type, chimeric or single site-mutated A alpha chains, with reciprocal interchanges between Ak and Ab. We then measured the stimulation of the T hybridomas in response to the transfectants. The results indicate that the hybridomas recognize diverse and complex determinants, with contributions from both A alpha and A beta chains, and from several regions or amino acids of the A alpha chain. The data are most consistent with a model in which alloreactivity results from the presentation of peptides to the T cell by an allogeneic MHC molecule, peptides that cannot be presented by the responder's own MHC complexes. The specificity of allorecognition seems to be imparted mainly by peptide/MHC molecule rather than TCR/MHC molecule contacts.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Felix, N. J., Suri, A., Walters, J. J., Horvath, S., Gross, M. L., Allen, P. M. (2006). I-Ep-Bound Self-Peptides: Identification, Characterization, and Role in Alloreactivity. J. Immunol. 176: 1062-1071 [Abstract] [Full Text]  
• Santambrogio, L., Sato, A. K., Fischer, F. R., Dorf, M. E., Stern, L. J. (1999). Abundant empty class II MHC molecules on the surface of immature dendritic cells. Proc. Natl. Acad. Sci. USA 96: 15050-15055 [Abstract] [Full Text]  
• Dellabona, P., Peccoud, J., Benoist, C., Mathis, D. (1989). T-cell Recognition of Superantigens: Inside or Outside the Groove?. Cold Spring Harb Symp Quant Biol 54: 375-381 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS