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International Immunology, Vol. 11, No. 6, 967-977, June 1999
© 1999 Japanese Society for Immunology

Characterization of the interaction of a TCR {alpha} chain variable domain with MHC II I-A molecules

Ayub Qadri1,2, Jayant Thatte1,3, Caius G. Radu1, Bertram Ober1,4 and E. Sally Ward1

1 Center for Immunology and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-8576, USA

Correspondence to: E. S. Ward

The {alpha}ß TCR recognizes peptides bound to MHC molecules. In the present study, we analyzed the interaction of a soluble TCR {alpha} chain variable domain (V{alpha}4.2–J{alpha}40; abbreviated to V{alpha}4.2) with the MHC class II molecule I-Au. V{alpha}4.2 bound specifically to I-Au expressed on the surface of a transfected thymoma cell line. Modifications in the amino acid residues located within the three complementarity-determining regions (CDRs) of the V{alpha} domain did not markedly affect this interaction. However, mutation of glutamic acid to alanine at position 69 of the fourth hypervariable region (HV4{alpha}) significantly increased the binding. Antibody inhibition studies suggested that the binding site was partly contributed by a region of the ß chain of I-Au. Furthermore, the binding of V{alpha}4.2 to the MHC molecule was dependent on the nature of the peptide bound in the groove. Soluble V{alpha}4.2 specifically inhibited the activation of TCR transfectants by I-Au-expressing cells pulsed with an N-terminal peptide of myelin basic protein. V{alpha}4.2 also bound to MHC class II-expressing spleen cell populations from mice of the H-2u and H-2d haplotypes. The binding of V{alpha}4.2 to I-A molecules might explain the immunoregulatory effects reported previously for TCR {alpha} chains. This V{alpha}4.2 interaction may also be relevant to models of antigen presentation involving the binding of intact proteins to MHC class II molecules followed by their processing to generate epitopes suitable for T cell recognition.

Keywords: fourth hypervariable region, immunosuppression, MHC class II, TCR, V{alpha} domain

2 Present address: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India

3 Present address: Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA

4 Present address: Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, 924 East 57th Street, 4th Floor, Chicago, IL 60637-5420, USA

Transmitting editor: C. Martinez-A


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[Abstract] [Full Text] [PDF]


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