June 10, 2020
Antigen presentation is essential for development of a robust immune response. Binding of an MHC-peptide complex by a T cell receptor is the initial and critical step for starting a new adaptive immune response or for regulating an ongoing one. Identification of effectively presented antigens is therefore a defining element for any successful immune therapy. Antigen presentation can occur through MHC class I, class II, or non-classical MHC proteins. Each protein complex has characteristic tissue expression, type of antigen peptide presented, and role in the immune response. Most lymphocytes including all of those with antigen presenting functions can express both MHC I and MHC II, and involvement of both MHC I- and MHC II-restricted responses is considered essential for a full immune response. Non-classical MHC such as HLA-E and HLA-G are characterized by either a relatively restricted tissue distribution or antigen presentation repertoire and have specific roles to play in the establishment of robust immunity.
Direct observation of presented peptides by mass spectrometry has become required for novel epitope discovery. This approach is the most physiologically relevant way to detect the modified and unmodified peptides presented by any type of MHC. Additionally, mass spectrometry can be used to quantitate the peptide presentation to ensure that attractive targets are sufficiently expressed to trigger an immune reaction. The limiting factor has now become the quality of the mass spectrometry data generated. This presentation will show examples of direct identification of novel presented peptides as well as survey the requirements for the industrialization of antigen presentation mass spectrometry to generate robust, reliable and quantitative measurements.
With an understanding that antigen presentation is required to initiate an immune response we will discuss how to use this information in therapeutics development. Designing a good immune therapy requires that the antigen is specific to the targeted pathology, as well as immunogenic. Those factors are especially relevant for modern immune therapies that seek to engage the host response as part of the complete therapy. Antigen presentation by mass spectrometry should therefore be embedded in a broader, integrated, characterization of host immunity. Specific characterizations include evaluation of wider host antigen presentation to assess target specificity, monitoring the status of the host microenvironment, as well as host immune exhaustion before and after antigen dosing to better understand the capacity to respond to the therapy. This presentation will depict case studies addressing each of these components of successful immune therapy candidates that start with successful antigen presentation.
Antigen presentation is the initial critical element, but for successful immune therapy development, antigen presentation should be embedded in an integrated assessment of host immunity
Speaker: Eustache Paramithiotis PhD, Vice-President, Research & Development, Caprion Biosciences Inc.