The Journal of Immunology, Vol 154, Issue 10 5153-5164, Copyright © 1995 by American Association of Immunologists

ARTICLES

Requirement for peptide in alloreactive CD4+ T cell recognition of class II MHC molecules

DA Weber, NK Terrell, Y Zhang, G Strindberg, J Martin, A Rudensky and NS Braunstein
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

To examine the role of peptide in alloreactive class II MHC-restricted responses, we transfected I-A molecules into the Ag-processing defective mutant cell line, T2. Consistent with their defective Ag- processing phenotype, the T2 transfectants predominantly express SDS- unstable I-A molecules on their surface. These cells and phenotypically normal APCs were used to study primary and secondary alloreactive T cell responses in limiting dilution assays. The results demonstrate that the majority of CD4 T cells that participate in primary alloresponses and essentially all the CD4 T cells that participate in secondary alloresponses recognize I-A conformers that depend on the presence of peptide and do not recognize the SDS-unstable I-A expressed by T2 transfectants. To further investigate the requirement for peptide in these responses, we incubated the T2 transfectants with E alpha 52- 68 peptide and generated SDS-stable I-A-peptide complexes on the cell surface. The I-Ab-E alpha peptide complexes expressed on T2 cells are stimulatory in secondary alloresponses if the T cells were exposed to the same I-A peptide complex during the priming step. These studies demonstrate that peptide-containing class II MHC is the relevant ligand for alloreactive T cells, and identify an alloreactive response to a peptide (E alpha 52-68) derived from a highly expressed cell surface "self" Ag, the I-E molecule.

This article has been cited by other articles:

				N. J. Felix, A. Suri, J. J. Walters, S. Horvath, M. L. Gross, and P. M. Allen I-Ep-Bound Self-Peptides: Identification, Characterization, and Role in Alloreactivity J. Immunol., January 15, 2006; 176(2): 1062 - 1071. [Abstract] [Full Text] [PDF]

				J. Andrassy, S. Kusaka, E. Jankowska-Gan, J. R. Torrealba, L. D. Haynes, B. R. Marthaler, R. C. Tam, B. M.-W. Illigens, N. Anosova, G. Benichou, et al. Tolerance to Noninherited Maternal MHC Antigens in Mice J. Immunol., November 15, 2003; 171(10): 5554 - 5561. [Abstract] [Full Text] [PDF]

				R. J. Hogan, J. VanBeek, D. R. Broussard, S. L. Surman, and D. L. Woodland Identification of MHC Class II-Associated Peptides That Promote the Presentation of Toxic Shock Syndrome Toxin-1 to T Cells J. Immunol., June 1, 2001; 166(11): 6514 - 6522. [Abstract] [Full Text] [PDF]

				G. Foucras, J. D. Coudert, C. Coureau, and J.-C. Guery Dendritic Cells Prime In Vivo Alloreactive CD4 T Lymphocytes Toward Type 2 Cytokine- and TGF-{beta}-Producing Cells in the Absence of CD8 T Cell Activation J. Immunol., November 1, 2000; 165(9): 4994 - 5003. [Abstract] [Full Text] [PDF]

				W. P. Thayer, J. R. Kraft, S. M. Tompkins, J. C. Moore IV, and P. E. Jensen Assessment of the Role of Determinant Selection in Genetic Control of the Immune Response to Insulin in H-2b Mice J. Immunol., September 1, 1999; 163(5): 2549 - 2554. [Abstract] [Full Text] [PDF]

				S. K. Mendiratta, J.-P. Kovalik, S. Hong, N. Singh, W. D. Martin, and L. Van Kaer Peptide dependency of alloreactive CD4+ T cell responses Int. Immunol., March 1, 1999; 11(3): 351 - 360. [Abstract] [Full Text] [PDF]

				R. E. Vance, J. R. Kraft, J. D. Altman, P. E. Jensen, and D. H. Raulet Mouse CD94/NKG2A Is a Natural Killer Cell Receptor for the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule Qa-1b J. Exp. Med., November 16, 1998; 188(10): 1841 - 1848. [Abstract] [Full Text] [PDF]

				C. Daniel, A. Grakoui, and P. M. Allen Inhibition of an In Vitro CD4+ T Cell Alloresponse Using Altered Peptide Ligands J. Immunol., April 1, 1998; 160(7): 3244 - 3250. [Abstract] [Full Text] [PDF]

				P. A. Smith, A. Brunmark, M. R. Jackson, and T. A. Potter Peptide-independent Recognition by Alloreactive Cytotoxic T Lymphocytes (CTL) J. Exp. Med., March 17, 1997; 185(6): 1023 - 1034. [Abstract] [Full Text] [PDF]