The Major Histocompatibility Complex (MHC) class I transplantation antigens functions as restriction elements for the presentation of viral and foreign antigens to the T cell receptor. Antigen is presented to the T cell receptor in the form of a peptide which binds within the helical bordered cleft of the class I molecule. However, the molecular interactions involved in the presentation of the peptide antigen by class I or its subsequent recognition as a target structure for the T cell receptor are not fully understood. Preliminary results presented in this proposal provide evidence that the class I molecule is structurally flexible and susceptible to structural perturbations induced by beta-2 microglobulin, a 12 Kd protein non-covalently associated with class i at the cell surface. This proposal will outline an experimental plan designed to address the role of class I structural flexibility and the relationship it has to class I function. Specifically, the role of beta- 2 microglobulin to overall class I structure and function will be intimately investigated. Discerning the role of beta-2 microglobulin in Class I structure will provide insight on the ability of class I to bind and present a vast array of disparate antigenic peptides to the T cell receptor.
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