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Cleavage of hemagglutinin from influenza A, at varying pH and over a twenty-four hour time period in the presence of cathepsin B, H and S

ABSTRACT: Pathogen-derived peptides presented by MHCII that are best able to activate cognate CD4+ T cells and initiate an adaptive immune response are termed immunodominant. The exact mechanisms and molecular determinants of antigen processing that contribute to immunodominance remain unclear. Recently, attention has been called to the events of proteolytic cleavage as a potential determinant. Here, we compare data generated through cleavage of hemagglutinin from influenza A, at varying pH and over a twenty-four hour time period in the presence of cathepsin B, H and S, to an immunodominant hierarchy previously established with an ex-vivo mouse model. We show that cleavage alone does not directly predict immunodominance, however resistance to digestion emerged as a determinant of immunodominance. Moreover, pH conditions contribute to shaping the peptidome available for MHCII binding and the size of the pools of unique peptides associated with immunodominance. These differences suggest the presence of multiple antigen processing pathways through which resistance to proteolytic cleavage and peptide redundancy may result in a more diverse peptidome for presentation.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Influenza A Virus (a/new Caledonia/20-jy2/1999(h1n1))

TISSUE(S): Organism Or Virus Or Viroid

DISEASE(S): Influenza

SUBMITTER: Greg Sabat

LAB HEAD: Dr. Thomas Kuhn

PROVIDER: PXD027327 | Pride | 2021-08-16

REPOSITORIES: Pride

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