REQUIREMENTS FOR CLASS I RESTRICTED E CELL RECOGNITION OF ANTIGEN

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While there is data to suggest that both class I and II_restricted antigenic determinants are present on short peptides, little more is known about the mechanism of antigen processing and presentation for class I restricted recognition of antigen. Our preliminary data indicate that class I-restricted cytolytic T cells (CTL) cAn be generated to the soluble protein antigen ovalbumin (OVA) when the antigen is used in the form of peptides present in a OVA tryptic digest but not when used as an intact protein. We will use OVA, which is well characterized with respect to the processing and presentation pathway for class II restricted responses and which is available in large quantities in pure forms, as a model to investigate the processing and presentation of antigen in the context of class I molecules. The parameters that influences the ability of OVA to induce class I-restricted CTL activity in vivo will be investigated in order to determine whether antigenic peptides can be administered directly to the animal or whether there is a need for an antigen "priming" cell. We will determine if the presence of an antigen containing a "helper determinant", perhaps linked to the class I-restricted determinant, enhances CTL priming. We will define the peptides within OVA that generate class I restricted responses and investigate the capacity of these peptides to form complexes with their class I restriction elements. Finally, we will investigate whether antigen processing for the generation of class I vs. class II restricted determinants involve the same or different metabolic pathways.