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The alpha 3 domain of the Qa-2 molecule is defective for CD8 binding and cytotoxic T lymphocyte activation.
- Source :
-
The Journal of experimental medicine [J Exp Med] 1993 Dec 01; Vol. 178 (6), pp. 2139-45. - Publication Year :
- 1993
-
Abstract
- Qa-2 is a nonclassical class I molecule encoded by the Q7 gene within the mouse major histocompatibility complex (MHC). Results from previous experiments on Qa-2, and on a chimeric Ld molecule (LQ3) in which the alpha 3 domain is encoded by Q7b, suggested that the alpha 3 domain of Qa-2 does not carry out the functions typical of the alpha 3 domains in other classical and nonclassical class I antigens. Class I molecules that contain the Qa-2 alpha 3 domain are poorly recognized by primary cytotoxic T lymphocytes (CTLs), and do not function normally in either positive or negative selection in vivo. By employing a cell-cell adhesion assay we demonstrate directly that the Qa-2 alpha 3 domain in the context of the LQ3 hybrid molecule cannot bind to human CD8, although other mouse class I alpha 3 domains bind efficiently. In addition, CD8-dependent CTL-mediated lysis of target cells, in a system which requires mouse CD8-class I alpha 3 domain interactions, is deficient in cells that express the Qa-2 alpha 3 domain. When combined with our earlier work on LQ3 transgenic mice, these results provide additional molecular support for the hypothesis that interaction with CD8 is required for both positive and negative selection of class I restricted T cells in the thymus. As the Qa-2 alpha 3 domain sequence does not differ from the previously defined minimal CD8 binding sequence of other class I molecules, these results also suggest that additional amino acids in the alpha 3 domain must be critical for CD8 binding and CTL activation.
- Subjects :
- Amino Acid Sequence
Animals
Cell Adhesion
Cytotoxicity, Immunologic
Histocompatibility Antigens Class I chemistry
Histocompatibility Antigens Class I metabolism
Humans
Lymphocyte Activation
Mice
Molecular Sequence Data
Recombinant Proteins metabolism
Sequence Alignment
Sequence Homology, Amino Acid
CD8 Antigens metabolism
Histocompatibility Antigens Class I immunology
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 178
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 8245786
- Full Text :
- https://doi.org/10.1084/jem.178.6.2139