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Interactions of murine MCH D(b) class I molecules with immunogenic peptides, beta2-microglobulin and the T cell receptor
Abstract
The development of new techniques for the study of the biology of MHC class I molecules are described. These techniques were applied to study several aspects of the murine $\rm D\sp{b}$ MHC class I molecule. The first technique, called CPEIA, allows for the study of peptide class I-interaction at the cell surface of the mutant cell line RMA-S. However, CPEIA has applications other than the study of MHC class I molecules. CPEIA was used to evaluate the role of the of $\rm D\sp{b}$ binding motif XXXXNXXX(I, M) as a determinant of peptide-$\rm D\sp{b}$ interaction, and to assess the importance of peptide-class I stability and affinity in the selection of immunodominant epitopes. These studies indicate that the presence of the motif does not, by itself, predict peptide-class I binding, and that peptide-class I stability, and, therefore, affinity, may have an important role in epitope selection. The role of non-anchor residues of the peptide sequence in the overall affinity of the peptide-class I interaction was then evaluated. These studies indicated that every position in the peptide sequence plays a role in modulating the affinity of the class I-peptide interaction. The second technique is an assay to study the interaction of purified MHC class I molecules with immunogenic peptides, $\beta$2-microglobulin ($\beta$2m), and the T cell receptor (TCR). The results obtained indicate that the peptide not only induces $\alpha 1-\alpha2$ domain refolding, as has already been shown, but it also induces refolding of the more distal $\alpha$3 domain. This finding may have implications in class I release from calnexin and the TAP transporter. Furthermore, these studies indicate the $\beta$2m is not necessary for peptide binding but augments signaling through the TCR. That $\beta$2m induces cytotoxic T cell activation has already been observed. However, it has been suggested that this occurs because $\beta$2m stabilizes pre-existing class I-peptide complexes or promotes the formation of new ones. The results presented here indicate that $\beta$2m might play a more direct role in TCR signaling.
Subject Area
Immunology|Molecular biology
Recommended Citation
Sigal, Luis Javier, "Interactions of murine MCH D(b) class I molecules with immunogenic peptides, beta2-microglobulin and the T cell receptor" (1994). ETD collection for University of Nebraska-Lincoln. AAI9510980.
https://digitalcommons.unl.edu/dissertations/AAI9510980