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

Qadri, Ayub, Thatte, Jayant, Radu, Caius G., Ober, Bertram and Ward, E. Sally (1999) Characterization of the interaction of a TCR α chain variable domain with MHC II I-A molecules. International Immunology, 11 (6), 967-977. (doi:10.1093/intimm/11.6.967).

Abstract

The αβ TCR recognizes peptides bound to MHC molecules. In the present study, we analyzed the interaction of a soluble TCR α chain variable domain (V(α)4.2-J(α)40; abbreviated to V(α)4.2) with the MHC class II molecule I-A(u). V(α)4.2 bound specifically to I-A(u) 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(α) domain did not markedly affect this interaction. However, mutation of glutamic acid to alanine at position 69 of the fourth hypervariable region (HV4α) significantly increased the binding. Antibody inhibition studies suggested that the binding site was partly contributed by a region of the β chain of I-A(u). Furthermore, the binding of V(α)4.2 to the MHC molecule was dependent on the nature of the peptide bound in the groove. Soluble V(α)4.2 specifically inhibited the activation of TCR transfectants by I-A(u)-expressing cells pulsed with an N-terminal peptide of myelin basic protein. V(α)4.2 also bound to MHC class II-expressing spleen cell populations from mice of the H-2(u) and H-2(d) haplotypes. The binding of V(α)4.2 to I-A molecules might explain the immunoregulatory effects reported previously for TCR α chains. This V(α)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.

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Contributors

Author: E. Sally Ward

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