The α3 domain of the Qa-2 molecule is defective for CD8 binding and cytotoxic T lymphocyte activation

Michael Teitell, Hilde Holcombe, Hilde Cheroutre, Caria J. Aldrich, Iwona Stroynowski, James Forman, Mitchell Kronenberg

Research output: Contribution to journalArticle

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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 α3 domain is encoded by Q7b, suggested that the α3 domain of Qa-2 does not carry out the functions typical of the α3 domains in other classical and nonclassical class I antigens. Class I molecules that contain the Qa-2 α3 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 α3 domain in the context of the LQ3 hybrid molecule cannot bind to human CD8, although other mouse class I α3 domains bind efficiently. In addition, CD8-dependent CTL-mediated lysis of target cells, in a system which requires mouse CD8-class I α3 domain interactions, is deficient in cells that express the Qa-2 α3 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 α3 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 α3 domain must be critical for CD8 binding and CTL activation.

Original languageEnglish (US)
Pages (from-to)2139-2145
Number of pages7
JournalJournal of Experimental Medicine
Volume178
Issue number6
StatePublished - Dec 1 1993

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Cytotoxic T-Lymphocytes
Lymphocyte Activation
Histocompatibility Antigens Class I
Major Histocompatibility Complex
Cell Adhesion
Thymus Gland
Transgenic Mice
T-Lymphocytes
Amino Acids
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

The α3 domain of the Qa-2 molecule is defective for CD8 binding and cytotoxic T lymphocyte activation. / Teitell, Michael; Holcombe, Hilde; Cheroutre, Hilde; Aldrich, Caria J.; Stroynowski, Iwona; Forman, James; Kronenberg, Mitchell.

In: Journal of Experimental Medicine, Vol. 178, No. 6, 01.12.1993, p. 2139-2145.

Research output: Contribution to journalArticle

Teitell, M, Holcombe, H, Cheroutre, H, Aldrich, CJ, Stroynowski, I, Forman, J & Kronenberg, M 1993, 'The α3 domain of the Qa-2 molecule is defective for CD8 binding and cytotoxic T lymphocyte activation', Journal of Experimental Medicine, vol. 178, no. 6, pp. 2139-2145.
Teitell, Michael ; Holcombe, Hilde ; Cheroutre, Hilde ; Aldrich, Caria J. ; Stroynowski, Iwona ; Forman, James ; Kronenberg, Mitchell. / The α3 domain of the Qa-2 molecule is defective for CD8 binding and cytotoxic T lymphocyte activation. In: Journal of Experimental Medicine. 1993 ; Vol. 178, No. 6. pp. 2139-2145.
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