Qa-1 interaction and T cell recognition of the Qa-1 determinant modifier peptide

Cotterill, L. A., Stauss, H. J., Millrain, M. M., Pappin, D. J., Rahman, D., Canas, B., Chandler, P., Stackpoole, A., Simpson, E., Robinson, P. J., Dyson, P. J. (September 1997) Qa-1 interaction and T cell recognition of the Qa-1 determinant modifier peptide. European Journal of Immunology, 27 (9). pp. 2123-32. ISSN 1521-4141 (Electronic)0014-2980 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9341749
DOI: 10.1002/eji.1830270902

Abstract

The peptide-binding properties of the nonclassical major histocompatibility complex (MHC) class 1b molecule Qa-1 were investigated using a transfected hybrid molecule composed of the alpha 1 and alpha 2 domains of Qa-1b and the alpha 3 domain of H-2Db. This allowed the use of a monoclonal antibody directed against H-2Db whilst retaining the peptide-binding groove of Qa-1b. By comparison with classical MHC class I molecules, intracellular maturation of the chimeric molecule was inefficient with weak intracellular association with beta 2-microglobulin. However, at the cell surface the hybrid molecules were stably associated with beta 2-microglobulin and were recognized by cytotoxic T lymphocyte (CTL) clones specific for the Qa-1b-presented peptide Qdm (AMAPRTLLL). A whole-cell binding assay was used to determine which residues of Qdm were important for binding to Qa-1b and CTL clones served to identify residues important for T cell recognition. Substitutions at position 1 and 5 did not reduce the efficiency of binding and had little effect on CTL recognition. In contrast, substitutions at position 9 resulted in loss of MHC class I binding. Mass spectrometric analysis of peptides eluted from immunopurified Qa-1b/Db molecules indicated that Qdm was the dominant peptide. The closely related peptide, AMVPRTLLL, which is derived from the signal sequence of H-2Dk, was also present, although it was considerably less abundant. The mass profile suggested the presence of additional peptides the majority of which consisted of eight to ten amino acid residues. Finally, the finding that a peptide derived from Klebsiella pneumoniae can bind raises the possibility that this non-classical MHC class I molecule may play a role in the presentation of peptides of microorganisms.

Item Type: Paper
Additional Information: Cotterill, L A Stauss, H J Millrain, M M Pappin, D J Rahman, D Canas, B Chandler, P Stackpoole, A Simpson, E Robinson, P J Dyson, P J Research Support, Non-U.S. Gov't Germany European journal of immunology Eur J Immunol. 1997 Sep;27(9):2123-32.
Uncontrolled Keywords: Amino Acid Sequence Animals Epitope Mapping H-2 Antigens/immunology Histocompatibility Antigens Class I/ immunology Mice Molecular Sequence Data Peptides/immunology Recombinant Fusion Proteins/immunology Recombinant Proteins/immunology T-Lymphocytes/ immunology beta 2-Microglobulin/metabolism
Subjects: bioinformatics > genomics and proteomics > design > protein network design > peptide design
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells

bioinformatics > genomics and proteomics > small molecules
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Kathleen Darby
Date: September 1997
Date Deposited: 07 May 2014 16:22
Last Modified: 07 May 2014 16:22
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30016

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