HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by García-Peydró, M. Articles by Castro, J. A. L. d. Search for Related Content PubMed PubMed Citation Articles by García-Peydró, M. Articles by Castro, J. A. L. d.

Antagonism of Direct Alloreactivity of an HLA-B27-Specific CTL Clone by Altered Peptide Ligands of Its Natural Epitope¹

Marina García-Peydró^*, Alberto Paradela^*, Juan P. Albar and José A. López de Castro^2,*

^* Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Cientificas), Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, Madrid, Spain; and Immunology and Oncology Department, Pharmacia-Consejo Superior de Investigaciones Cientificas, Centro Nacional de Biotecnología, Cantoblanco, Madrid, Spain

Antagonism of allospecific CTL by altered MHC ligands is a potential approach to specific immunomodulation of allogeneic T cell responses in acute graft rejection and graft-vs-host disease. In this study we have analyzed the capacity of peptide analogs of a natural HLA-B27-allospecific CTL epitope to antagonize direct alloreactivity. Alanine scanning demonstrated that positions 4, 5, and 7 of the peptide epitope were critical for allorecognition. A number of relatively conservative substitutions at each of these positions were then tested for their effect on allorecognition and antagonism. All substitutions at position 5 abrogated cytotoxicity. In contrast, a few changes at positions 4 and 7 were tolerated, indicating a limited flexibility of the allospecific CTL in recognition of peptide epitope variants. Most of the substitutions impairing cytotoxicity actually induced antagonism. However, whereas epitope variants with changes at positions 4 and 7 behaved as weak or intermediate antagonists, some of the variants with changes at position 5 antagonized CTL alloreactivity almost completely. The results in this study demonstrate for the first time that antagonism of direct class I-mediated alloreactivity can be achieved by variants of a natural allospecific peptide epitope.

This article has been cited by other articles:

				L. K. Ely, K. J. Green, T. Beddoe, C. S. Clements, J. J. Miles, S. P. Bottomley, D. Zernich, L. Kjer-Nielsen, A. W. Purcell, J. McCluskey, et al. Antagonism of Antiviral and Allogeneic Activity of a Human Public CTL Clonotype by a Single Altered Peptide Ligand: Implications for Allograft Rejection J. Immunol., May 1, 2005; 174(9): 5593 - 5601. [Abstract] [Full Text] [PDF]

				A. C. Karlsson, S. G. Deeks, J. D. Barbour, B. D. Heiken, S. R. Younger, R. Hoh, M. Lane, M. Sallberg, G. M. Ortiz, J. F. Demarest, et al. Dual Pressure from Antiretroviral Therapy and Cell-Mediated Immune Response on the Human Immunodeficiency Virus Type 1 Protease Gene J. Virol., June 15, 2003; 77(12): 6743 - 6752. [Abstract] [Full Text] [PDF]

				S. Reinelt, M. Marti, S. Dedier, T. Reitinger, G. Folkers, J. A. L. de Castro, and D. Rognan beta -Amino Acid Scan of a Class I Major Histocompatibility Complex-restricted Alloreactive T-cell Epitope J. Biol. Chem., June 29, 2001; 276(27): 24525 - 24530. [Abstract] [Full Text] [PDF]